Journal articles on the topic 'Non-insulin-dependent diabetes – Animal models'
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Shafrir, Eleazar. "Animal models of non-insulin-dependent diabetes." Diabetes / Metabolism Reviews 8, no. 3 (October 1992): 179–208. http://dx.doi.org/10.1002/dmr.5610080302.
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Pierce, G. J., T. G. Maddaford, and J. C. Russell. "Cardiovascular dysfunction in insulin-dependent and non-insulin-dependent animal models of diabetes mellitus." Canadian Journal of Physiology and Pharmacology 75, no. 4 (April 1, 1997): 343–50. http://dx.doi.org/10.1139/y97-027.
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Wong, F. Susan, and Charles A. Janeway. "Insulin-dependent diabetes mellitus and its animal models." Current Opinion in Immunology 11, no. 6 (December 1999): 643–47. http://dx.doi.org/10.1016/s0952-7915(99)00031-x.
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Peterson, Jeffrey D., and Kathryn Haskins. "Immunotherapy of animal models of insulin-dependent diabetes mellitus." Current Opinion in Endocrinology and Diabetes 2, no. 1 (February 1995): 17–23. http://dx.doi.org/10.1097/00060793-199502000-00004.
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Miyazaki, J. I., and F. Tashiro. "Transgenic Models of Insulin-Dependent Diabetes Mellitus." ILAR Journal 35, no. 2 (January 1, 1993): 37–41. http://dx.doi.org/10.1093/ilar.35.2.37.
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Bohlen, H. G., and J. M. Lash. "Endothelial-dependent vasodilation is preserved in non-insulin-dependent Zucker fatty diabetic rats." American Journal of Physiology-Heart and Circulatory Physiology 268, no. 6 (June 1, 1995): H2366—H2374. http://dx.doi.org/10.1152/ajpheart.1995.268.6.h2366.
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Alterations in the structural properties of the microvasculature and in vasodilation mediated by endothelial- and, to some extent, nonendothelial-dependent mechanisms occurs in insulin-dependent diabetic humans and animals. Less severe problems of this type appear to occur during non-insulin-dependent diabetes mellitus (NIDDM) in humans, but data based on animal models of NIDDM are not available. The endothelial- and nonendothelial-mediated dilation of intestinal arterioles was studied in insulin-resistant male Zucker fatty diabetic (DB) rats and their lean normal male littermates (LM) at ages 22-25 and 35-40 wk. DB become hyperglycemic (450-550 mg/100 ml) at age 9-10 wk. Microiontophoretic release of acetylcholine, ADP, and nitroprusside onto arterioles caused equivalent dilation in LM and DB for both large and intermediate diameter arterioles. Administration of streptozotocin (STZ) to DB at age 18-19 wk lowered their insulin concentration approximately 25% but did not significantly effect the resting plasma glucose concentration. However, endothelial-dependent vasodilation was attenuated by 70-80% within 8-10 wk. The overall results indicate that prolonged hyperglycemia in insulin-resistant but hyperinsulinemic rats does not impair the endothelial- and nonendothelial-dependent dilation of the intestinal microvasculature. However, compromising beta-cell function with STZ, as indicated by lowering the insulin concentration by one-fourth, substantially compromises endothelial-dependent dilation similar to that found in insulin-dependent diabetic rats and humans.
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Fabregat, M. E., A. Novials, M. H. Giroix, A. Sener, R. Gomis, and W. J. Malaisse. "Pancreatic Islet Mitochondrial Glycerophosphate Dehydrogenase Deficiency in Two Animal Models of Non-Insulin-Dependent Diabetes Mellitus." Biochemical and Biophysical Research Communications 220, no. 3 (March 1996): 1020–23. http://dx.doi.org/10.1006/bbrc.1996.0525.
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Takeshita, Noritaka, Hitoshi Ishida, Taizo Yamamoto, Gyohan Koh, Takeshi Kurose, Kazuo Tsuji, Yoshimasa Okamoto, Hitoshi Ikeda, and Yutaka Seino. "Circulating levels and bone contents of bone γ-carboxyglutamic acid-containing protein in rat models of non-insulin-dependent diabetes mellitus." Acta Endocrinologica 128, no. 1 (January 1993): 69–73. http://dx.doi.org/10.1530/acta.0.1280069.
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In order to investigate the pathophysiology of the diabetic osteopenia observed in non-insulin-dependent diabetes mellitus, the circulating levels and the bone contents of bone γ-carboxyglutamic acid-containing protein (osteocalcin) were determined in rat models of non-insulin-dependent diabetes mellitus, neonatally streptozotocin-induced rats and in genetic Wistar fatty rats. In Wistar fatty rats the plasma level of osteocalcin was 8.1±0.8 nmol/l, significantly lower than the value of 1 7.3±0.9 nmol/l in their lean littermates (p<0.001). Bone length, bone strength, and weight of powdered bone in Wistar fatty rats were significantly decreased compared to control rats (p<0.001, p<0.02 and p<0.001, respectively). Bone content of osteocalcin per femur in Wistar fatty rats was also significantly decreased compared to controls (p<0.001). In addition, plasma osteocalcin in neonatally streptozotocin-induced diabetic rats was 2.9±0.3 nmol/l, which was also significantly decreased compared to the value of 5.6±0.5 nmol/l in their controls (p<0.001). Since it has been established that the plasma level of osteocalcin is well related to bone formation and turnover, the low plasma values in these animal models suggest that bone formation and turnover are decreased in non-insulin-dependent diabetes mellitus. Low bone formation and turnover are, therefore, postulated to be one of the pathophysiological characteristics of the skeletal tissue in non-insulin-dependent diabetes mellitus, and to be at least in part responsible for the occurrence of this complication.
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Aleixandre de Artiñano, Amaya, and Marta Miguel Castro. "Experimental rat models to study the metabolic syndrome." British Journal of Nutrition 102, no. 9 (July 27, 2009): 1246–53. http://dx.doi.org/10.1017/s0007114509990729.
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Being the metabolic syndrome a multifactorial condition, it is difficult to find adequate experimental models to study this pathology. The obese Zucker rats, which are homozygous for the fa allele, present abnormalities similar to those seen in human metabolic syndrome and are a widely extended model of insulin resistance. The usefulness of these rats as a model of non-insulin-dependent diabetes mellitus is nevertheless questionable, and they neither can be considered a clear experimental model of hypertension. Some experimental models different from the obese Zucker rats have also been used to study the metabolic syndrome. Some derive from the spontaneously hypertensive rats (SHR). In this context, the most important are the obese SHR, usually named Koletsky rats. Hyperinsulinism, associated with either normal or slightly elevated levels of blood glucose, is present in these animals, but SHR/N-corpulent rats are a more appropriated model of non-insulin-dependent diabetes mellitus. The SHR/NDmc corpulent rats, a subline of SHR/N-corpulent rats, also exhibit metabolic and histopathologic characteristics associated with human metabolic disorders. A new animal model of the metabolic syndrome, stroke-prone–SHR (SHRSP) fatty rats, was obtained by introducing a segment of the mutant leptin receptor gene from the Zucker line heterozygous for the fa gene mutation into the genetic background of the SHRSP. Very recently, it has been developed as a non-obese rat model with hypertension, fatty liver and characteristics of the metabolic syndrome by transgenic overexpression of a sterol-regulatory element-binding protein in the SHR rats. The Wistar Ottawa Karlsburg W rats are also a new strain that develops a nearly complete metabolic syndrome. Moreover, a new experimental model of low-capacity runner rats has also been developed with elevated blood pressure levels together with the other hallmarks of the metabolic syndrome.
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Freund, P., H. P. Wolff, and H. F. Kühnle. "(−)-BM 13.0913: A new oral antidiabetic agent that improves insulin sensitivity in animal models of type II (non—insulin-dependent) diabetes mellitus." Metabolism 44, no. 5 (May 1995): 570–76. http://dx.doi.org/10.1016/0026-0495(95)90112-4.
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Madhusudhan, Thati, and Wolfram Ruf. "Coagulation Signalling and Metabolic Disorders: Lessons Learned from Animal Models." Hämostaseologie 39, no. 02 (May 27, 2019): 164–72. http://dx.doi.org/10.1055/s-0039-1688800.
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AbstractNutrient excess in obesity drives metabolic reprogramming in multiple tissues involving extensive interorgan and intercellular crosstalk. Experimental and clinical studies show that prolonged nutrient excess often compromises metabolic adaptation propagating proobesogenic and proinflammatory responses. Chronic inflammation further promotes insulin resistance and associated comorbidities. Obesity and type 2 diabetes are characterized by a hypercoagulable state and clinical studies show a strong correlation of markers of coagulation activation in metabolic disorders. Coagulation protease-dependent signalling via protease-activated receptors is intimately associated with inflammation. The experimental evidence supports roles of tissue factor and G protein coupled protease-activated receptor-2 signalling in the regulation of insulin resistance and metabolic inflammation in diet-induced obesity. Likewise, increases in plasminogen activator inhibitor-1 levels and fibrin-driven inflammation promote insulin resistance in obesity. Additionally, impaired thrombomodulin-dependent protein C activation is mechanistically linked to diabetic kidney disease. Given the increased usage of direct oral anticoagulants, understanding the role of specific coagulation proteases in regulation of metabolic inflammation is highly relevant and might provide insights into the design of novel treatment regimens for patients suffering from thromboinflammatory and cardiometabolic disorders.
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Hulin, Bernard, Peter A. McCarthy, and E. Michael Gibbs. "The Glitazone Family of Antidiabetic Agents." Current Pharmaceutical Design 2, no. 1 (February 1996): 85–102. http://dx.doi.org/10.2174/1381612802666220920215821.
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Abstract: In 1982, Takeda Inc. reported the discovery of ciglitazone (5-[4-(l methylcyclohexylmethoxy)-benzyl]thiazolidine-2,4-dione, ADD-3878), a compound which lowers blood glucose in animal models of Non Insulin Dependent Diabetes without an increase in insulin release, and which does not have an effect on the glycemia in normal animals. Since then many analogs have been produced, including troglitazone, pioglitazone, englitazone and darglitazone, and compounds where the thiazolidinedione ring has been replaced by other acidic moieties. Pharmacological studies have revealed effects on gluconeogenesis, glucose transport and glucose transporter expression, and a putative receptor in fat cells, PPARy, has been proposed. Clinical studies on troglitazone and darglitazone have shown these compounds to have glucose lowering effects, as well as effects on insulin sensitivity, lipid levels and blood pressure.
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Valitsky, Michael, Amnon Hoffman, Terry Unterman, and Jacob Bar-Tana. "Insulin sensitizer prevents and ameliorates experimental type 1 diabetes." American Journal of Physiology-Endocrinology and Metabolism 313, no. 6 (December 1, 2017): E672—E680. http://dx.doi.org/10.1152/ajpendo.00329.2016.
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Insulin-dependent type-1 diabetes (T1D) is driven by autoimmune β-cell failure, whereas systemic resistance to insulin is considered the hallmark of insulin-independent type-2 diabetes (T2D). In contrast to this canonical dichotomy, insulin resistance appears to precede the overt diabetic stage of T1D and predict its progression, implying that insulin sensitizers may change the course of T1D. However, previous attempts to ameliorate T1D in animal models or patients by insulin sensitizers have largely failed. Sensitization to insulin by MEthyl-substituted long-chain DICArboxylic acid (MEDICA) analogs in T2D animal models surpasses that of current insulin sensitizers, thus prompting our interest in probing MEDICA in the T1D context. MEDICA efficacy in modulating the course of T1D was verified in streptozotocin (STZ) diabetic rats and autoimmune nonobese diabetic (NOD) mice. MEDICA treatment normalizes overt diabetes in STZ diabetic rats when added on to subtherapeutic insulin, and prevents/delays autoimmune T1D in NOD mice. MEDICA treatment does not improve β-cell insulin content or insulitis score, but its efficacy is accounted for by pronounced total body sensitization to insulin. In conclusion, potent insulin sensitizers may counteract genetic predisposition to autoimmune T1D and amplify subtherapeutic insulin into an effective therapeutic measure for the treatment of overt T1D.
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Yang, Yang, and Pere Santamaria. "Lessons on autoimmune diabetes from animal models." Clinical Science 110, no. 6 (May 15, 2006): 627–39. http://dx.doi.org/10.1042/cs20050330.
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T1DM (Type I diabetes mellitus) results from selective destruction of the insulin-producing β-cells of the pancreas by the immune system, and is characterized by hyperglycaemia and vascular complications arising from suboptimal control of blood glucose levels. The discovery of animal models of T1DM in the late 1970s and early 1980s, particularly the NOD (non-obese diabetic) mouse and the BB (BioBreeding) diabetes-prone rat, had a fundamental impact on our ability to understand the genetics, aetiology and pathogenesis of this disease. NOD and BB diabetes-prone rats spontaneously develop a form of diabetes that closely resembles the human counterpart. Early studies of these animals quickly led to the realization that T1DM is caused by autoreactive T-lymphocytes and revealed that the development of T1DM is controlled by numerous polymorphic genetic elements that are scattered throughout the genome. The development of transgenic and gene-targeting technologies during the 1980s allowed the generation of models of T1DM of reduced genetic and pathogenic complexity, and a more detailed understanding of the immunogenetics of T1DM. In this review, we summarize the contribution of studies in animal models of T1DM to our current understanding of four fundamental aspects of T1DM: (i) the nature of genetic elements affording T1DM susceptibility or resistance; (ii) the mechanisms underlying the development and recruitment of pathogenic autoreactive T-cells; (iii) the identity of islet antigens that contribute to the initiation and/or progression of islet inflammation and β-cell destruction; and (iv) the design of avenues for therapeutic intervention that are rooted in the knowledge gained from studies of animal models. Development of new animal models will ensure continued progress in these four areas.
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Nichols, C. G., and J. C. Koster. "Diabetes and insulin secretion: whither KATP?" American Journal of Physiology-Endocrinology and Metabolism 283, no. 3 (September 1, 2002): E403—E412. http://dx.doi.org/10.1152/ajpendo.00168.2002.
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The critical involvement of ATP-sensitive potassium (KATP) channels in insulin secretion is confirmed both by the demonstration that mutations that reduce KATP channel activity underlie many if not most cases of persistent hyperinsulinemia, and by the ability of sulfonylureas, which inhibit KATP channels, to enhance insulin secretion in type II diabetics. By extrapolation, we contend that mutations that increase β-cell KATP channel activity should inhibit glucose-dependent insulin secretion and underlie, or at least predispose to, a diabetic phenotype. In transgenic animal models, this prediction seems to be borne out. Although earlier genetic studies failed to demonstrate a linkage between KATP mutations and diabetes in humans, recent studies indicate significant association of KATP channel gene mutations or polymorphisms and type II diabetes. We suggest that further efforts to understand the involvement of KATP channels in diabetes are warranted.
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Ionut, Viorica, Huiwen Liu, Vahe Mooradian, Ana Valeria B. Castro, Morvarid Kabir, Darko Stefanovski, Dan Zheng, Erlinda L. Kirkman, and Richard N. Bergman. "Novel canine models of obese prediabetes and mild type 2 diabetes." American Journal of Physiology-Endocrinology and Metabolism 298, no. 1 (January 2010): E38—E48. http://dx.doi.org/10.1152/ajpendo.00466.2009.
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Human type 2 diabetes mellitus (T2DM) is often characterized by obesity-associated insulin resistance (IR) and β-cell function deficiency. Development of relevant large animal models to study T2DM is important and timely, because most existing models have dramatic reductions in pancreatic function and no associated obesity and IR, features that resemble more T1DM than T2DM. Our goal was to create a canine model of T2DM in which obesity-associated IR occurs first, followed by moderate reduction in β-cell function, leading to mild diabetes or impaired glucose tolerance. Lean dogs ( n = 12) received a high-fat diet that increased visceral (52%, P < 0.001) and subcutaneous (130%, P < 0.001) fat and resulted in a 31% reduction in insulin sensitivity (SI) (5.8 ± 0.7 × 10−4 to 4.1 ± 0.5 × 10−4 μU·ml−1·min−1, P < 0.05). Animals then received a single low dose of streptozotocin (STZ; range 30–15 mg/kg). The decrease in β-cell function was dose dependent and resulted in three diabetes models: 1) frank hyperglycemia (high STZ dose); 2) mild T2DM with normal or impaired fasting glucose (FG), 2-h glucose >200 mg/dl during OGTT and 77–93% AIRg reduction (intermediate dose); and 3) prediabetes with normal FG, normal 2-h glucose during OGTT and 17–74% AIRg reduction (low dose). Twelve weeks after STZ, animals without frank diabetes had 58% more body fat, decreased β-cell function (17–93%), and 40% lower SI. We conclude that high-fat feeding and variable-dose STZ in dog result in stable models of obesity, insulin resistance, and 1) overt diabetes, 2) mild T2DM, or 3) impaired glucose tolerance. These models open new avenues for studying the mechanism of compensatory changes that occur in T2DM and for evaluating new therapeutic strategies to prevent progression or to treat overt diabetes.
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Rodgers, BD, M. Bernier, and MA Levine. "Endocrine regulation of G-protein subunit production in an animal model of type 2 diabetes mellitus." Journal of Endocrinology 168, no. 3 (March 1, 2001): 509–15. http://dx.doi.org/10.1677/joe.0.1680509.
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Adipocyte beta-adrenergic sensitivity is compromised in animal models of obesity and type 2 diabetes. Although changes in the membrane concentrations of G-protein alpha subunits (Galpha) have been implicated, it remains to be determined how these changes are affected by insulin resistance in the different animal models. Because previous studies used young animals, we measured the concentrations of Galpha and Gbeta subunits in epididymal fat from aged (48 weeks old) db/db mice and from their lean littermates to more closely reproduce the model of type 2 diabetes mellitus. Levels of immunoreactive Galphas, Galphai(1/2), Galphao and Galphaq/11 were all significantly greater in adipocyte membranes from the db/db mice than in membranes from their lean non-diabetic littermate controls. Levels of Galphai(1) and Galphai(2) were also individually determined and although they appeared to be slightly higher in db/db membranes, these differences were not significant. Although the levels of both Galphas isoforms were elevated, levels of the 42 and 46 kDa proteins rose by approximately 42% and 20% respectively, indicating differential protein processing of Galphas. By contrast, levels of Galphai3 were similar in the two groups. The levels of common Gbeta and Gbeta2 were also elevated in db/db mice, whereas Gbeta1 and Gbeta4 levels were not different. To determine whether these changes were due to insulin resistance per se or to elevated glucocorticoid production, G-protein subunit levels were quantified in whole cell lysates from 3T3-L1 adipocytes that were stimulated with different concentrations of either insulin or corticosterone. Although none of the subunit levels was affected by insulin, the levels of both Galphas isoforms were increased equally by corticosterone in a concentration-dependent manner. Since glucocorticoids are known regulators of Galphas gene expression in many cell types and in adipocytes from diabetic rodents, the results presented herein appear to more accurately reflect diabetic pathophysiology than do those of previous studies which report a decrease in Galphas levels. Taken together, these results indicate that most of the selective changes in G-protein subunit production in adipocytes from this animal model of type 2 diabetes may not be due to diminished insulin sensitivity, but may be due to other endocrine or metabolic abnormalities associated with the diabetic phenotype.
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Gvazava, I. G., A. V. Kosykh, O. S. Rogovaya, O. P. Popova, K. A. Sobyanin, A. K. Khrushchev, A. V. Timofeev, and E. A. Vorotelyak. "A Simplified Streptozotocin-Induced Diabetes Model in Nude Mice." Acta Naturae 12, no. 4 (December 22, 2020): 98–104. http://dx.doi.org/10.32607/actanaturae.11202.
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Preclinical studies of human cellular and tissue-based products (HCT/Ps) for transplantation therapy of type 1 diabetes mellitus (T1DM) necessarily involve animal models, particularly mouse models of diabetes induced by streptozotocin (STZ). These models should mimic the clinical and metabolic manifestations of T1DM in humans (face validity) and be similar to T1DM in terms of the pathogenetic mechanism (construct validity). Furthermore, since HCT/Ps contain human cells, modeling of diabetes in immune-deficient animals is obligatory. Here we describe the most simplified diabetes model in Nude mice. Diabetes was induced in 31 males by a single intraperitoneal injection of STZ in normal saline at a medium-to-high dose of 150 mg/kg body weight. Fourteen control animals received only saline. Non-fasting plasma glucose (PG) levels were measured periodically for 50 days. All STZ-treated mice survived beyond 50 days. By day 15 after STZ administration, 22 of 31 (71%) mice developed stable diabetes based on the following criteria: (1) non-fasting PG 15 mmol/L on consecutive measurements up until day 50; (2) no diabetes remission. The mean non-fasting PG in mice with stable diabetes over the period of 35 days was equal to 25.7 mmol/L. On day 50, mean plasma insulin concentration, mean pancreatic insulin content, and the average number of -cells in pancreatic islets were 2.6, 8.4, and 50 times lower, respectively, than in the control animals. We consider that our Nude mouse model of diabetes meets face validity and construct validity criteria and can be used in preclinical studies of HCT/Ps.
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Sato, Mayumi, Takaaki Tai, Yoshiki Nunoura, Yukiko Yajima, Seiichi Kawashima, and Keiji Tanaka. "Dehydrotrametenolic Acid Induces Preadipocyte Differentiation and Sensitizes Animal Models of Noninsulin-Dependent Diabetes Mellitus to Insulin." Biological & Pharmaceutical Bulletin 25, no. 1 (2002): 81–86. http://dx.doi.org/10.1248/bpb.25.81.
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Tan, Sze Jun, Badiah Baharin, Nurulhuda Mohd, and Syed Nabil. "Effect of Anti-Diabetic Medications on Dental Implants: A Scoping Review of Animal Studies and Their Relevance to Humans." Pharmaceuticals 15, no. 12 (December 5, 2022): 1518. http://dx.doi.org/10.3390/ph15121518.
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Animal studies have ascertained that hyperglycemia adversely affects bone metabolism and dental implant osseointegration. However, diabetic patients show low occurrence of unfavorable hard or soft peri-implant tissue changes, differences that are possibly due to treatment with anti-diabetic medications. This scoping review aimed to systematically examine the effects of these drugs on implant outcomes and explore the predictive modality of animal studies for clinical practice according to type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Three electronic databases (MEDLINE, EBSCOHost, and Cochrane) were searched according to the PRISMA-ScR standards for studies on diabetic animals that received titanium implants and anti-diabetic treatments. Risk assessment was performed using the SYRCLE Risk-of-Bias (RoB) tool. Twenty-one papers were included, encompassing six types of medications. Fifteen studies were on T1DM animals, and only six involved T2DM models. T1DM animals were treated with non-insulin drugs in four investigations, while insulin was utilized in 11 other studies. In T2DM experiments, five administered non-insulin drugs, and only one applied locally delivered insulin. Only insulin in T1DM studies produced a positive influence on bone-implant contact (BIC), bone mineral content, and removal torque values. Inappropriate drug selection, inadequate glycemic control, and high RoB depict a mismatch between the research focus and the translational rationale to clinical practice. There remains a knowledge gap regarding T2DM investigations due to the lack of studies. More data are needed concerning intraoral implants and the performance of osseointegrated implants in patients with a later onset of diabetes. Future research should reflect the pathophysiology and treatment of each type of diabetes to ensure clinical applicability.
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Arakawa, Kenji, Tomomi Ishihara, Masamichi Aoto, Masanori Inamasu, Akira Saito, and Katsuo Ikezawa. "Actions of novel antidiabetic thiazolidinedione, T-174, in animal models of non-insulin-dependent diabetes mellitus (NIDDM) and in cultured muscle cells." British Journal of Pharmacology 125, no. 3 (October 1998): 429–36. http://dx.doi.org/10.1038/sj.bjp.0702066.
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Djohan, Djohan. "EFFECTIVENESS OF TOMATO (SOLANUM LYCOPERSICUM) NANOHERBAL AS ANTIHYPERGLYCEMIA IN STREPTOZOTOCIN INDUCED DIABETIC RAT." Jambura Journal of Health Sciences and Research 4, no. 3 (August 12, 2022): 859–68. http://dx.doi.org/10.35971/jjhsr.v4i3.13760.
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Diabetes merupakan penyakit kronis yang terjadi di saat insulin yang diproduksi oleh tubuh tidak bisa digunakan secara efektif maupun organ pankreas mengalami masalah dimana insulin tidak dapat diproduksi sebagaimana mestinya. Kebaruan penelitian ini karena meneliti tentang efektivitas nanoherbal tomat (solanum lycopersicum) sebagai antihiperglikemia pada tikus diabetes yang terinduksi streptozotocin. Penelitian ini bertujuan untuk secara sistematis menganalisis dan meninjau hewan dan penelitian pada tikus putih yang diinduksi STZ. Metode pencarian elektronik dilakukan dengan mencari MEDLINE melalui platform PubMed, Web of Science, Embase melalui platform Ovid, CINAHL, dan Scopus. Penulis juga akan mencari literatur kelabu seperti makalah konferensi, laporan teknis, tesis, dan disertasi di Google Scholar, Google, OpenGrey, ProQuest Disertasi Tesis, dan British Library Ethos. Penulis mencari setiap database hingga November 2021 menggunakan kata kunci MeSH. Istilah pencarian dibagi menjadi tiga komponen, yaitu komponen populasi yang meliputi kata-kata “hewan”, “model hewan”, “studi praklinis”, “hewan percobaan”, “hewan percobaan”, “hewan laboratorium, ” "tikus", "kelinci", "tikus diabetes", "model penyakit hewan". Komponen intervensi dengan kata-kata “Solanum Lycopersicum” “tomat,” dan “nano herbal,” Akhirnya, istilah komponen penyakit akan menjadi "diabetes mellitus, tipe 2," "diabetes mellitus tidak tergantung insulin," "NIDDM," "gangguan metabolisme glukosa," "penyakit metabolik," "hiperlipidemia," "hiperglikemia," "insulin resistensi," dan "intoleransi glukosa." Hasilnya menunjukkan bahwa Efektifitas Nanoherbal tomat (Solanum Lycopersicum) sebagai Antihiperglikemia pada tikus diabetes yang terinduksi Streptozotocin. Kesimpulan penelitiannya ada bukti praklinis bahwa Solanum Lycopersicum efektif dalam menurunkan gula darah tinggi.Kata kunci: Diabetes; Streptozotocin; Tomat.AbstractDiabetes is a chronic disease that occurs when the insulin produced by the body cannot be used effectively or the pancreas has problems where insulin cannot be produced properly. The novelty of this study is that it examines the effectiveness of tomato nanoherbal (Solanum lycopersicum) as an antihyperglycemic agent in streptozotocin-induced diabetic rats. This review aims to systematically analyze and review animals and studies in STZ-induced white mice. An electronic search was carried out by searching for MEDLINE through the PubMed platform, Web of Science, Embase through the Ovid, CINAHL, and Scopus platforms. Authors will also search for gray literature such as conference papers, technical reports, theses, and dissertations on Google Scholar, Google, Open Grey, ProQuest Dissertations Theses, and British Library Ethos. The author searched each database until November 2021 using the keyword MeSH. The search term is divided into three components, namely a population component which includes the words “animal”, “animal model”, “preclinical study”, “experimental animal”, “experimental animal”, “laboratory animal,” “rat”, “rabbit ", "diabetic mice", "animal disease models". The intervention component with the words “Solanum Lycopersicum” “tomato,” and “nano herbal,” Finally, the disease component term would be “diabetes mellitus, type 2,” “non-insulin dependent diabetes mellitus,” “NIDDM,” “metabolic disorder. glucose," "metabolic disease," "hyperlipidemia," "hyperglycemia," "insulin resistance," and "glucose intolerance." The results showed that the effectiveness of Tomato (Solanum Lycopersicum) Nanoherbal as Antihyperglycemia in Streptozotocin-induced diabetic rat. The conclusion of the study is that there is preclinical evidence that Solanum Lycopersicum is effective in lowering high blood sugar.
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Lautt, W. Wayne. "Insulin Sensitivity in Skeletal Muscle Regulated by a Hepatic Hormone, HISS." Canadian Journal of Applied Physiology 30, no. 3 (June 1, 2005): 304–12. http://dx.doi.org/10.1139/h05-123.
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The current state of the HISS (hepatic insulin sensitizing substance) hypothesis is briefly outlined. In the postmeal absorptive state, 50-60% of the glucose storage action of insulin is accounted for by the actions of HISS released from the liver and acting on skeletal muscle. Hepatic parasympathetic nerves permissively regulate the ability of a pulse of insulin to release HISS, thereby potentiating the impact of insulin in the fed state. HISS release in response to insulin decreases progressively with fasting to create a physiological state of HISS-dependent insulin resistance. HISS release is regulated by parasympathetic nerves via muscarinic receptors and nitric oxide, and insulin resistance of skeletal muscle produced by hepatic denervation is reversed by intraportal but not intravenous acetylcholine or a nitric oxide donor. It is suggested that HISS-dependent insulin resistance occurs in animal models including sucrose-fed rats, spontaneously hypertensive rats, chronic liver disease, fetal alcohol effect in the adult offspring, and type 2 diabetes. Key words: insulin resistance, RIST, parasympathetic nerves, liver, diabetes
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Chan, Catherine B. "β-Cell stimulus–secretion coupling defects in rodent models of obesity." Canadian Journal of Physiology and Pharmacology 73, no. 10 (October 1, 1995): 1414–24. http://dx.doi.org/10.1139/y95-197.
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Hyperinsulinemia accompanies obesity in human patients and experimental rodent models and exacerbates insulin resistance, but the causes of increased insulin secretion remain obscure. This review examines progress in defining biochemical and molecular β-cell defects that have been elucidated in the past 5 years. Some defects, such as decreased glucose transport, decreased mitochondrial FAD-linked glycerophosphate dehydrogenase activity, and altered anomeric specificity for glucose, become evident only after onset of non-insulin-dependent diabetes mellitus. Thus, these defects are unlikely to play a role in the pathogenesis of hyperinsulinemia in obesity. Other biochemical changes, including increased glucokinase and (or) hexokinase function, increased glucose cycling, and altered regulation of intracellular Ca2+ are present in obese nondiabetic animals and may therefore contribute to development of hyperinsulinemia. Few developmental studies have been performed to correlate onset of defects with environmentally and genetically mediated control mechanisms of β-cell function. However, the availability of new molecular biology techniques should facilitate identification of factors causing hyperinsulinemia in obesity.Key words: obesity, insulin secretion, islets of Langerhans, rodent models, stimulus–secretion coupling.
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Funk, Deanna R., Normand G. Boulé, Peter A. Senior, and Jane E. Yardley. "Does exercise pose a challenge to glucoregulation after clinical islet transplantation?" Applied Physiology, Nutrition, and Metabolism 42, no. 1 (January 2017): 1–7. http://dx.doi.org/10.1139/apnm-2016-0402.
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Islet transplantation (ITx) is effective in preventing severe hypoglycemia by restoring glucose-dependent insulin secretion in type 1 diabetes (T1D), but may not normalize glucose regulation. Studies suggest that physical activity plays a role in maintaining β-cell mass and function in individuals with type 2 diabetes and animal models of diabetes. This could indicate that physical activity plays a role in graft survival in ITx recipients. This review’s objective is to assess current knowledge related to physical activity in ITx recipients. Responses to other challenges in blood glucose control (i.e., hypoglycemia) in human ITx recipients were examined to provide in-depth background information. To identify studies involving exercise in ITx recipients, a systematic search was performed using PubMed, Medline, and Embase, which revealed 277 English language publications. Publications were excluded if they did not involve ITx recipients; did not involve physical activity or hypoglycemia; or did not report on glucose, insulin, or counterregulatory hormones. During induced hypoglycemia, studies indicate normal suppression of insulin in ITx individuals compared with healthy non-T1D controls. Studies involving exercise in ITx animals have conflicting results, with time since transplantation and transplantation site (spleen, liver, kidney, peritoneal cavity) as possible confounders. No study examining blood glucose responses to physical activity in human ITx recipients was identified. A small number of induced-hypoglycemia studies in humans, and exercise studies in animals, would suggest that glucoregulation is greatly improved yet is still imperfect in this population and that ITx does not fully restore counterregulatory responses to challenges in blood glucose homeostasis.
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Misra, Tarun, James S. C. Gilchrist, James C. Russell, and Grant N. Pierce. "Cardiac myofibrillar and sarcoplasmic reticulum function are not depressed in insulin-resistant JCR:LA-cp rats." American Journal of Physiology-Heart and Circulatory Physiology 276, no. 6 (June 1, 1999): H1811—H1817. http://dx.doi.org/10.1152/ajpheart.1999.276.6.h1811.
Full textAbstract:
Depressed myofibrillar Ca2+-ATPase activity and sarcoplasmic reticulum (SR) Ca2+ uptake are important mechanisms that are responsible for the cardiac dysfunction exhibited by insulin-deficient (type I) diabetic animals. The JCR:LA- cp rat is a model for type II non-insulin-dependent diabetes mellitus (NIDDM). This rat is insulin resistant, obese, and has high levels of circulating glucose, cholesterol, insulin, and triglycerides. The purpose of this study was to determine whether changes in cardiac myofibrillar, SR, and cardiomyocyte function exist in this model of type II diabetes. Myofibrils and SR were isolated from hearts by differential centrifugation. Surprisingly, we found that myofibrillar Ca2+-ATPase activities were unaltered in these animals. Ca2+uptake in isolated SR fractions was increased in diabetic cp/ cprats, whereas Ca2+-ATPase activity and ryanodine binding were unchanged. Cardiomyocytes isolated from hearts of control and experimental animals had similar active cell shortening and intracellular Ca2+concentration under basal conditions and in response to caffeine. Our data argue against the presence of a cardiomyopathy in this diabetic model and suggest that insulin may be an important factor in the cardiomyopathy observed in type I diabetic models.
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Ann Ellis, E., and Maria B. Grant. "Oxidative Stress in Galactose Induced Diabetic Retinopathy in Inducible Nitric Oxide Synthase Knockout Mice." Microscopy and Microanalysis 7, S2 (August 2001): 638–39. http://dx.doi.org/10.1017/s1431927600029263.
Full textAbstract:
Oxidative stress and inducible nitric oxide synthase (iNOS) have been implicated in endothelial cell dysfunction in diabetic retinopathy by formation of peroxynitrite, a cytotoxic product of superoxide and high levels of nitric oxide. Spontaneous diabetic models do not allow for separating the oxidative stress as a result of hyperglycemia from that of the nitric oxide system. in addition chemicals such as streptozotocin which can induce diabetes in animal models cause oxidative stress and induce iNOS before the onset of hyperglycemia. Galactose has been used to induce non-insulin dependent diabetes in mice and rats while gene knockout mice provide a means to study the role of specific NOS components. This study used cytochemical localization of hydrogen peroxide produced by NADH oxidase, a marker for superoxide production, and immunocytochemical localization of nitrotyrosine, a marker for nitric oxide formed radical peroxynitrite, to investigate the role of oxidative stress and the nitric oxide system in galactose induced diabetic retinopathy in iNOS knockout (iNOS%) mice.
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Ostler, Joseph E., Santosh K. Maurya, Justin Dials, Steve R. Roof, Steven T. Devor, Mark T. Ziolo, and Muthu Periasamy. "Effects of insulin resistance on skeletal muscle growth and exercise capacity in type 2 diabetic mouse models." American Journal of Physiology-Endocrinology and Metabolism 306, no. 6 (March 15, 2014): E592—E605. http://dx.doi.org/10.1152/ajpendo.00277.2013.
Full textAbstract:
Type 2 diabetes mellitus is associated with an accelerated muscle loss during aging, decreased muscle function, and increased disability. To better understand the mechanisms causing this muscle deterioration in type 2 diabetes, we assessed muscle weight, exercise capacity, and biochemistry in db/ db and TallyHo mice at prediabetic and overtly diabetic ages. Maximum running speeds and muscle weights were already reduced in prediabetic db/ db mice when compared with lean controls and more severely reduced in the overtly diabetic db/ db mice. In contrast to db/ db mice, TallyHo muscle size dramatically increased and maximum running speed was maintained during the progression from prediabetes to overt diabetes. Analysis of mechanisms that may contribute to decreased muscle weight in db/ db mice demonstrated that insulin-dependent phosphorylation of enzymes that promote protein synthesis was severely blunted in db/ db muscle. In addition, prediabetic (6-wk-old) and diabetic (12-wk-old) db/ db muscle exhibited an increase in a marker of proteasomal protein degradation, the level of polyubiquitinated proteins. Chronic treadmill training of db/ db mice improved glucose tolerance and exercise capacity, reduced markers of protein degradation, but only mildly increased muscle weight. The differences in muscle phenotype between these models of type 2 diabetes suggest that insulin resistance and chronic hyperglycemia alone are insufficient to rapidly decrease muscle size and function and that the effects of diabetes on muscle growth and function are animal model-dependent.
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Chen, Hong, Beatriz Dardik, Ling Qiu, Xianglin Ren, Shari L. Caplan, Bryan Burkey, Brian R. Boettcher, and Jesper Gromada. "Cevoglitazar, a Novel Peroxisome Proliferator-Activated Receptor-α/γ Dual Agonist, Potently Reduces Food Intake and Body Weight in Obese Mice and Cynomolgus Monkeys." Endocrine Reviews 31, no. 3 (June 1, 2010): 404–5. http://dx.doi.org/10.1210/edrv.31.3.9995.
Full textAbstract:
ABSTRACT Cevoglitazar is a dual agonist for the peroxisome proliferator-activated receptor (PPAR)-α and -γ subtypes. Dual activation of PPARα and -γ is a therapeutic approach in development for the treatment of type 2 diabetes mellitus and diabetic dyslipidemia. In this report, we show that, in addition to improving insulin sensitivity and lipid metabolism like other dual PPAR agonists, cevoglitazar also elicits beneficial effects on energy homeostasis in two animal models of obesity. In leptin-deficient ob/ob mice, administration of cevoglitazar at 0.5, 1, or 2 mg/kg for 18 d led to acute and sustained, dose-dependent reduction of food intake and body weight. Furthermore, plasma levels of glucose and insulin were normalized after 7 d of cevoglitazar treatment at 0.5 mg/kg. Plasma levels of free fatty acids and triglycerides were dose-dependently reduced. In obese and insulin-resistant cynomolgus monkeys, treatment with cevoglitazar at 50 and 500 μg/kg for 4 wk lowered food intake and body weight in a dose-dependent manner. In these animals, cevoglitazar also reduced fasting plasma insulin and, at the highest dose, reduced hemoglobin A1c levels by 0.4%. These preclinical results demonstrate that cevoglitazar holds promise for the treatment of diabetes and obesity-related disorders because of its unique beneficial effect on energy balance in addition to improving glycemic and metabolic control.
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Forsberg, Elisabete A., Ileana R. Botusan, Jing Wang, Verena Peters, Ishrath Ansurudeen, Kerstin Brismar, and Sergiu Bogdan Catrina. "Carnosine decreases IGFBP1 production in db/db mice through suppression of HIF-1." Journal of Endocrinology 225, no. 3 (April 13, 2015): 159–67. http://dx.doi.org/10.1530/joe-14-0571.
Full textAbstract:
IGF binding protein 1 (IGFBP1) is a member of the binding proteins for the IGF with an important role in glucose homeostasis. Circulating IGFBP1 is derived essentially from the liver where it is mainly regulated negatively by insulin. Carnosine, a natural antioxidant, has been shown to improve metabolic control in different animal models of diabetes but its mechanisms of action are still not completely unraveled. We therefore investigate the effect of carnosine treatment on the IGFBP1 regulation in db/db mice. Db/db mice and heterozygous non-diabetic mice received for 4 weeks regular water or water supplemented with carnosine.Igfbp1mRNA expression in the liver was evaluated using qPCR and the protein levels in plasma by western blot. Plasma IGF1 and insulin were analyzed using immunoassays. HepG2 cells were used to study thein vitroeffect of carnosine on IGFBP1. The modulation of hypoxia inducible factor-1 alpha (HIF-1α) which is the central mediator of hypoxia-induction of IGFBP1 was analyzed using: WB, reporter gene assay and qPCR. Carnosine decreased the circulating IGFBP1 levels and the liver expressionIgfbp1, through a complex mechanism acting both directly by suppressing the HIF-1α-mediated IGFBP1 induction and indirectly through increasing circulating insulin level followed by a decrease in the blood glucose levels and increased the plasma levels or IGF1. Reduction of IGFBP1 in diabetes through insulin-dependent and insulin-independent pathways is a novel mechanism by which carnosine contributes to the improvement of the metabolic control in diabetes.
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Chen, Hong, Beatriz Dardik, Ling Qiu, Xianglin Ren, Shari L. Caplan, Bryan Burkey, Brian R. Boettcher, and Jesper Gromada. "Cevoglitazar, a Novel Peroxisome Proliferator-Activated Receptor-α/γ Dual Agonist, Potently Reduces Food Intake and Body Weight in Obese Mice and Cynomolgus Monkeys." Endocrinology 151, no. 7 (May 19, 2010): 3115–24. http://dx.doi.org/10.1210/en.2009-1366.
Full textAbstract:
Cevoglitazar is a dual agonist for the peroxisome proliferator-activated receptor (PPAR)-α and -γ subtypes. Dual activation of PPARα and -γ is a therapeutic approach in development for the treatment of type 2 diabetes mellitus and diabetic dyslipidemia. In this report, we show that, in addition to improving insulin sensitivity and lipid metabolism like other dual PPAR agonists, cevoglitazar also elicits beneficial effects on energy homeostasis in two animal models of obesity. In leptin-deficient ob/ob mice, administration of cevoglitazar at 0.5, 1, or 2 mg/kg for 18 d led to acute and sustained, dose-dependent reduction of food intake and body weight. Furthermore, plasma levels of glucose and insulin were normalized after 7 d of cevoglitazar treatment at 0.5 mg/kg. Plasma levels of free fatty acids and triglycerides were dose-dependently reduced. In obese and insulin-resistant cynomolgus monkeys, treatment with cevoglitazar at 50 and 500 μg/kg for 4 wk lowered food intake and body weight in a dose-dependent manner. In these animals, cevoglitazar also reduced fasting plasma insulin and, at the highest dose, reduced hemoglobin A1c levels by 0.4%. These preclinical results demonstrate that cevoglitazar holds promise for the treatment of diabetes and obesity-related disorders because of its unique beneficial effect on energy balance in addition to improving glycemic and metabolic control.
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Rosado, Juan A., Raquel Diez-Bello, Ginés M. Salido, and Isaac Jardin. "Fine-tuning of microRNAs in Type 2 Diabetes Mellitus." Current Medicinal Chemistry 26, no. 22 (September 20, 2019): 4102–18. http://dx.doi.org/10.2174/0929867325666171205163944.
Full textAbstract:
Type 2 diabetes mellitus is a metabolic disease widely spread across industrialized countries. Sedentary lifestyle and unhealthy alimentary habits lead to obesity, boosting both glucose and fatty acid in the bloodstream and eventually, insulin resistance, pancreas inflammation and faulty insulin production or secretion, all of them very well-defined hallmarks of type 2 diabetes mellitus. miRNAs are small sequences of non-coding RNA that may regulate several processes within the cells, fine-tuning protein expression, with an unexpected and subtle precision and in time-frames ranging from minutes to days. Since the discovery of miRNA and their possible implication in pathologies, several groups aimed to find a relationship between type 2 diabetes mellitus and miRNAs. Here we discuss the pattern of expression of different miRNAs in cultured cells, animal models and diabetic patients. We summarize the role of the most important miRNAs involved in pancreas growth and development, insulin secretion and liver, skeletal muscle or adipocyte insulin resistance in the context of type 2 diabetes mellitus.
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bone, A. J., C. S. T. Hii, D. Brown, W. Smith, and S. L. Howell. "Assessment of the antidiabetic activity of epicatechin in streptozotocin-diabetic and spontaneously diabetic BB/E rats." Bioscience Reports 5, no. 3 (March 1, 1985): 215–21. http://dx.doi.org/10.1007/bf01119590.
Full textAbstract:
(−)-Epicatechin has previously been suggested to rapidly reverse alloxan diabetes in rats. We have assessed the therapeutic value of the compound in two further animal models of insulin-dependent diabetes mellitus, namely streptozotocin – diabetic rats and the spontaneously diabetic BB/E rat. There was no indication of a reversal of established diabetes in either the streptozotocin-diabetic or the spontaneously diabetic BB/E rats. Moreover, epicatechin also failed to halt the progression of the disease in prediabetic BB/E rats. Earlier claims of the potential use of epicatechin as an antidiabetic agent must therefore be treated with some caution.
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Ishizuka, Tatsuo, Kazuo Kajita, Atsushi Miura, Masayoshi Ishizawa, Yoshinori Kanoh, Satomi Itaya, Mika Kimura, et al. "DHEA improves glucose uptake via activations of protein kinase C and phosphatidylinositol 3-kinase." American Journal of Physiology-Endocrinology and Metabolism 276, no. 1 (January 1, 1999): E196—E204. http://dx.doi.org/10.1152/ajpendo.1999.276.1.e196.
Full textAbstract:
We have examined the effect of adrenal androgen, dehydroepiandrosterone (DHEA), on glucose uptake, phosphatidylinositol (PI) 3-kinase, and protein kinase C (PKC) activity in rat adipocytes. DHEA (1 μM) provoked a twofold increase in 2-[3H]deoxyglucose (DG) uptake for 30 min. Pretreatment with DHEA increased insulin-induced 2-[3H]DG uptake without alterations of insulin specific binding and autophosphorylation of insulin receptor. DHEA also stimulated PI 3-kinase activity. [3H]DHEA bound to purified PKC containing PKC-α, -β, and -γ. DHEA provoked the translocation of PKC-β and -ζ from the cytosol to the membrane in rat adipocytes. These results suggest that DHEA stimulates both PI 3-kinase and PKCs and subsequently stimulates glucose uptake. Moreover, to clarify the in vivo effect of DHEA on Goto-Kakizaki (GK) and Otsuka Long-Evans fatty (OLETF) rats, animal models of non-insulin-dependent diabetes mellitus (NIDDM) were treated with 0.4% DHEA for 2 wk. Insulin- and 12- O-tetradecanoyl phorbol-13-acetate-induced 2-[3H]DG uptakes of adipocytes were significantly increased, but there was no significant increase in the soleus muscles in DHEA-treated GK/Wistar or OLETF/Long-Evans Tokushima (LETO) rats when compared with untreated GK/Wistar or OLETF/LETO rats. These results indicate that in vivo DHEA treatment can result in increased insulin-induced glucose uptake in two different NIDDM rat models.
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Schuurs, A. H. W. M., H. A. M. Verheul, and L. P. C. Schot. "Experimental work with anabolics in autoimmunity models." Acta Endocrinologica 110, no. 3_Suppla (December 1985): S97—S107. http://dx.doi.org/10.1530/acta.0.109s00097.
Full textAbstract:
Abstract. 19-nortestosterone (nandrolone) or its decanoate was tested in six animal models for autoimmune disease. The compound was found capable of inhibiting the development of disease symptoms or the deterioration of certain immune parameters in three out of five models of spontaneous autoimmune disease: NZB/NZW F1 (NZB/W) mice (lupus glomerulonephritis, Sjögren's disease-like syndrome), NZB (lupus glomerulonephritis, autoimmune haemolytic anaemia) and OS chickens (thyroiditis). No effect of the compound was seen in MRL lpr/lpr mice (lupus glomerulonephritis, lymphoproliferative disease) and in BB rats (insulin-dependent diabetes mellitus; IDDM). Nandrolone decanoate also seems to be active in myasthenia gravis evoked in rats immunised with acetylcholine receptor but further experiments are necessary to confirm this. In a first experiment also ethylestrenol was found to give favourable effects in the model.
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Min, Se Hee, Jinhee Kwon, Eun-Ju Do, So Hee Kim, Eun Sil Kim, Jin-Yong Jeong, Sang Mun Bae, Sang-Yeob Kim, and Do Hyun Park. "Duodenal Dual-Wavelength Photobiomodulation Improves Hyperglycemia and Hepatic Parameters with Alteration of Gut Microbiome in Type 2 Diabetes Animal Model." Cells 11, no. 21 (November 3, 2022): 3490. http://dx.doi.org/10.3390/cells11213490.
Full textAbstract:
Background: Recently, the duodenum has garnered interest for its role in treating metabolic diseases, including type 2 diabetes (T2DM). Multiple sessions of external photobiomodulation (PBM) in previous animal studies suggested it resulted in improved hyperglycemia, glucose intolerance, and insulin resistance with a multifactorial mechanism of action, despite the target organ of PBM not being clearly proven. This study aimed to determine whether a single session of a duodenal light-emitting diode (LED) PBM may impact the T2DM treatment in an animal model. Methods: Goto–Kakizaki rats as T2DM models were subjected to PBM through duodenal lumen irradiation, sham procedure, or control in 1-week pilot (630 nm, 850 nm, or 630/850 nm) and 4-week follow-up (630 nm or 630/850 nm) studies. Oral glucose tolerance tests; serum glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide, and insulin levels; liver chemistry and histology; and gut microbiome in the PBM, sham control, and control groups were evaluated. Results: In the 1-week study, duodenal dual-wavelength (D, 630/850 nm) LED PBM showed improved glucose intolerance, alkaline phosphatase and cholesterol levels, and weight gain than other groups. The D-LED PBM group in the 4-week study also showed improved hyperglycemia and liver enzyme levels, with relatively preserved pancreatic islets and increased serum insulin and GLP-1 levels. Five genera (Bacteroides, Escherichia, Parabacteroides, Allobaculum, and Faecalibaculum) were significantly enriched 1 week after the D-LED PBM. Bacteroides acidifaciens significantly increased, while Lachnospiraceae significantly decreased after 1 week. Conclusion: A single session of D-LED PBM improved hyperglycemia and hepatic parameters through the change of serum insulin, insulin resistance, insulin expression in the pancreatic β-cells, and gut microbiome in T2DM animal models.
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Diani, A. R., Geri Sawada, Beatrice Wyse, F. T. Murray, and Mehmood Khan. "Pioglitazone preserves pancreatic islet structure and insulin secretory function in three murine models of type 2 diabetes." American Journal of Physiology-Endocrinology and Metabolism 286, no. 1 (January 2004): E116—E122. http://dx.doi.org/10.1152/ajpendo.00331.2003.
Full textAbstract:
Thiazolidinediones may slow the progression of type 2 diabetes by preserving pancreatic β-cells. The effects of pioglitazone (PIO) on structure and function of β-cells in KKA(y), C57BL/6J ob/ob, and C57BL/KsJ db/db mice (genetic models of type 2 diabetes) were examined. ob/ob ( n = 7) and db/db ( n = 9) mice were randomly assigned to 50-125 mg·kg body wt-1·day-1of PIO in chow beginning at 6-10 wk of age. Control ob/ob ( n = 7) and db/db mice ( n = 9) were fed chow without PIO. KKA(y) mice ( n = 15) were fed PIO daily at doses of 62-144 mg·kg body wt-1·day-1. Control KKA(y) mice ( n = 10) received chow without PIO. Treatment continued until euthanasia at 14-26 wk of age. Blood was collected at baseline (before treatment) and just before euthanasia and was analyzed for glucose, glycosylated hemoglobin, and plasma insulin. Some of the splenic pancreas of each animal was resected and partially sectioned for light or electron microscopy. The remainder of the pancreas was assayed for insulin content. Compared with baseline and control groups, PIO treatment significantly reduced blood glucose and glycosylated hemoglobin levels. Plasma insulin levels decreased significantly in ob/ob mice treated with PIO. All groups treated with PIO exhibited significantly greater β-cell granulation, evidence of reduced β-cell stress, and 1.5- to 15-fold higher levels of pancreatic insulin. The data from these studies suggest that comparable effects would be expected to slow the progression of type 2 diabetes, either delaying or possibly preventing progression to an insulin-dependent state.
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Dimitrakoudis, D., M. Vranic, and A. Klip. "Effects of hyperglycemia on glucose transporters of the muscle: use of the renal glucose reabsorption inhibitor phlorizin to control glycemia." Journal of the American Society of Nephrology 3, no. 5 (November 1992): 1078–91. http://dx.doi.org/10.1681/asn.v351078.
Full textAbstract:
Individuals with non-insulin dependent or insulin-dependent diabetes mellitus present insulin resistance in peripheral tissues. This is reflected in a subnormal whole body insulin-dependent glucose utilization, largely dependent on skeletal muscle. Glucose transport across the cell membrane of this tissue is rate limiting in the utilization of the hexose. Therefore, it is possible that a defect exists in insulin-dependent glucose transport in skeletal muscle in diabetic states. This review focuses on two questions: is there a defect at the level of glucose transporters in skeletal muscle of diabetic animal models, and is this a consequence of abnormal insulin or glucose levels? The latter question arises from the fact that these parameters usually vary inversely to each other. Glucose transport into skeletal muscle occurs by two membrane proteins, the GLUT1 and GLUT4 gene products. By subcellular fractionation and Western blotting with isoform-specific antibodies, it was determined that isolated plasma membranes (PM) contain GLUT4 and GLUT1 proteins at a molar ratio of 3.5:1 and that an intracellular fraction (internal membranes; IM) different from sarcoplasmic reticulum contains only GLUT4 transporters. The IM furnishes transporters to the PM in response to insulin. Both transporter isoforms bind cytochalasin B in a D-glucose-protectable fashion. In streptozocin-induced diabetes of the rat with normal fasting insulin levels and marked hyperglycemia, the number of cytochalasin B-binding sites and of GLUT4 proteins diminishes in the PM whereas the GLUT1 proteins increase to a new ratio of about 1.5:1 GLUT4:GLUT1. In the IM, the levels of GLUT4 protein drop, as does the cellular GLUT4 mRNA. To investigate if these changes are associated with hyperglycemia, glucose levels were corrected back to normal values for a 24-h period with sc injections of phlorizin to block proximal tubule glucose reabsorption. This treatment restored cytochalasin B binding, restored GLUT4 and GLUT1 values back to normal levels in the PM, and partly restored cytochalasin B binding but not GLUT4 levels in the IM, consistent with only a partial recovery of GLUT4 mRNA. It is concluded that GLUT4 protein in the PM correlates inversely whereas GLUT1 protein correlates directly with glycemia. It is proposed that the decrease in GLUT4 levels is a protective mechanism, sparing skeletal muscle from gaining glucose and experiencing diabetic complications, albeit at the expense of becoming insulin resistant.(ABSTRACT TRUNCATED AT 400 WORDS)
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Zouhar, Petr, Günaj Rakipovski, Muhammad Hamza Bokhari, Oliver Busby, Johan F. Paulsson, Kilian W. Conde-Frieboes, Johannes J. Fels, et al. "UCP1-independent glucose-lowering effect of leptin in type 1 diabetes: only in conditions of hypoleptinemia." American Journal of Physiology-Endocrinology and Metabolism 318, no. 1 (January 1, 2020): E72—E86. http://dx.doi.org/10.1152/ajpendo.00253.2019.
Full textAbstract:
The possibility to use leptin therapeutically for lowering glucose levels in patients with type 1 diabetes has attracted interest. However, earlier animal models of type 1 diabetes are severely catabolic with very low endogenous leptin levels, unlike most patients with diabetes. Here, we aim to test glucose-lowering effects of leptin in novel, more human-like murine models. We examined the glucose-lowering potential of leptin in diabetic models of two types: streptozotocin-treated mice and mice treated with the insulin receptor antagonist S961. To prevent hypoleptinemia, we used combinations of thermoneutral temperature and high-fat feeding. Leptin fully normalized hyperglycemia in standard chow-fed streptozotocin-treated diabetic mice. However, more humanized physiological conditions (high-fat diets or thermoneutral temperatures) that increased adiposity — and thus also leptin levels — in the diabetic mice abrogated the effects of leptin, i.e., the mice developed leptin resistance also in this respect. The glucose-lowering effect of leptin was not dependent on the presence of the uncoupling protein-1 and was not associated with alterations in plasma insulin, insulin-like growth factor 1, food intake or corticosterone but fully correlated with decreased plasma glucagon levels and gluconeogenesis. An important implication of these observations is that the therapeutic potential of leptin as an additional treatment in patients with type 1 diabetes is probably limited. This is because such patients are treated with insulin and do not display low leptin levels. Thus, the potential for a glucose-lowering effect of leptin would already have been attained with standard insulin therapy, and further effects on blood glucose level through additional leptin cannot be anticipated.
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Pani, Arianna, Riccardo Giossi, Danilo Menichelli, Veronica Andrea Fittipaldo, Francesca Agnelli, Elvira Inglese, Alessandra Romandini, et al. "Inositol and Non-Alcoholic Fatty Liver Disease: A Systematic Review on Deficiencies and Supplementation." Nutrients 12, no. 11 (November 3, 2020): 3379. http://dx.doi.org/10.3390/nu12113379.
Full textAbstract:
Liver lipid accumulation is a hallmark of non-alcoholic fatty liver disease (NAFLD), broadly associated with insulin resistance. Inositols (INS) are ubiquitous polyols implied in many physiological functions. They are produced endogenously, are present in many foods and in dietary supplements. Alterations in INS metabolism seems to play a role in diseases involving insulin resistance such as diabetes and polycystic ovary syndrome. Given its role in other metabolic syndromes, the hypothesis of an INS role as a supplement in NAFLD is intriguing. We performed a systematic review of the literature to find preclinical and clinical evidence of INS supplementation efficacy in NAFLD patients. We retrieved 10 studies on animal models assessing Myoinosiol or Pinitol deficiency or supplementation and one human randomized controlled trial (RCT). Overall, INS deficiency was associated with increased fatty liver in animals. Conversely, INS supplementation in animal models of fatty liver reduced hepatic triglycerides and cholesterol accumulation and maintained a normal ultrastructural liver histopathology. In the one included RCT, Pinitol supplementation obtained similar results. Pinitol significantly reduced liver fat, post-prandial triglycerides, AST levels, lipid peroxidation increasing glutathione peroxidase activity. These results, despite being limited, indicate the need for further evaluation of INS in NAFLD in larger clinical trials.
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Hu, Junping, Janet D. Klein, Jie Du, and Xiaonan H. Wang. "Cardiac Muscle Protein Catabolism in Diabetes Mellitus: Activation of the Ubiquitin-Proteasome System by Insulin Deficiency." Endocrinology 149, no. 11 (July 24, 2008): 5384–90. http://dx.doi.org/10.1210/en.2008-0132.
Full textAbstract:
Protein degradation is increased by both insulin deficiency and insulin resistance in humans and animal models. In skeletal muscle this insulin-dependent increase in protein degradation involves activation of both caspase-3 and the ubiquitin-proteasome system. The influence of abnormal insulin signaling on protein metabolism in cardiac muscle is not well understood; therefore, we measured protein degradation in cardiac muscle of mice with streptozotocin-induced diabetes. Insulin deficiency increased both total muscle proteolysis (measured as tyrosine release in muscle slices or extracts) and the degradation of the myofibrillar protein actin (measured as the appearance of a 14-kDa actin fragment). Expression of ubiquitin mRNA and chymotrypsin-like activity in the proteasome were increased, indicating activation of the ubiquitin-proteasome system in diabetic mouse heart. We also evaluated possible signaling pathways that might regulate cardiac muscle proteolysis. Insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, and Akt phosphorylation were decreased. Insulin replacement prevented the decrease in IRS-1/Akt phosphorylation, the increase in proteolysis, and attenuated the increase in ubiquitin mRNA. We conclude that insulinopenia accelerates proteolysis in cardiac muscle by reducing IRS-1/Akt signaling, which leads to activation of the ubiquitin-proteasome proteolytic pathway.
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Fox, Todd E., Megan M. Young, Michelle M. Pedersen, Sarah Giambuzzi-Tussey, Mark Kester, and Thomas W. Gardner. "Insulin signaling in retinal neurons is regulated within cholesterol-enriched membrane microdomains." American Journal of Physiology-Endocrinology and Metabolism 300, no. 3 (March 2011): E600—E609. http://dx.doi.org/10.1152/ajpendo.00641.2010.
Full textAbstract:
Neuronal cell death is an early pathological feature of diabetic retinopathy. We showed previously that insulin receptor signaling is diminished in retinas of animal models of diabetes and that downstream Akt signaling is involved in insulin-mediated retinal neuronal survival. Therefore, further understanding of the mechanisms by which retinal insulin receptor signaling is regulated could have therapeutic implications for neuronal cell death in diabetes. Here, we investigate the role of cholesterol-enriched membrane microdomains to regulate PKC-mediated inhibition of Akt-dependent insulin signaling in R28 retinal neurons. We demonstrate that PKC activation with either a phorbol ester or exogenous application of diacylglycerides impairs insulin-induced Akt activation, whereas PKC inhibition augments insulin-induced Akt activation. To investigate the mechanism by which PKC impairs insulin-stimulated Akt activity, we assessed various upstream mediators of Akt signaling. PKC activation did not alter the tyrosine phosphorylation of the insulin receptor or IRS-2. Additionally, PKC activation did not impair phosphatidylinositol 3-kinase activity, phosphoinositide-dependent kinase phosphorylation, lipid phosphatase (PTEN), or protein phosphatase 2A activities. Thus, we next investigated a biophysical mechanism by which insulin signaling could be disrupted and found that disruption of lipid microdomains via cholesterol depletion blocks insulin-induced Akt activation and reduces insulin receptor tyrosine phosphorylation. We also demonstrated that insulin localizes phosphorylated Akt to lipid microdomains and that PMA reduces phosphorylated Akt. In addition, PMA localizes and recruits PKC isotypes to these cholesterol-enriched microdomains. Taken together, these results demonstrate that both insulin-stimulated Akt signaling and PKC-induced inhibition of Akt signaling depend on cholesterol-enriched membrane microdomains, thus suggesting a putative biophysical mechanism underlying insulin resistance in diabetic retinopathy.
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Kitamura. "Effects of Propolis Extract and Propolis-Derived Compounds on Obesity and Diabetes: Knowledge from Cellular and Animal Models." Molecules 24, no. 23 (December 1, 2019): 4394. http://dx.doi.org/10.3390/molecules24234394.
Full textAbstract:
Propolis is a natural product resulting from the mixing of bee secretions with botanical exudates. Since propolis is rich in flavonoids and cinnamic acid derivatives, the application of propolis extracts has been tried in therapies against cancer, inflammation, and metabolic diseases. As metabolic diseases develop relatively slowly in patients, the therapeutic effects of propolis in humans should be evaluated over long periods of time. Moreover, several factors such as medical history, genetic inheritance, and living environment should be taken into consideration in human studies. Animal models, especially mice and rats, have some advantages, as genetic and microbiological variables can be controlled. On the other hand, cellular models allow the investigation of detailed molecular events evoked by propolis and derivative compounds. Taking advantage of animal and cellular models, accumulating evidence suggests that propolis extracts have therapeutic effects on obesity by controlling adipogenesis, adipokine secretion, food intake, and energy expenditure. Studies in animal and cellular models have also indicated that propolis modulates oxidative stress, the accumulation of advanced glycation end products (AGEs), and adipose tissue inflammation, all of which contribute to insulin resistance or defects in insulin secretion. Consequently, propolis treatment may mitigate diabetic complications such as nephropathy, retinopathy, foot ulcers, and non-alcoholic fatty liver disease. This review describes the beneficial effects of propolis on metabolic disorders.
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Wolf, Eckhard. "GENETICALLY ENGINEERED PIG MODELS FOR TRANSLATIONAL DIABETES RESEARCH." Reproduction, Fertility and Development 25, no. 1 (2013): 320. http://dx.doi.org/10.1071/rdv25n1ab346.
Full textAbstract:
Animal models play crucial roles for understanding disease mechanisms and for the development and evaluation of therapeutic strategies. In biomedicine, classical rodent models are most widely used for several reasons, including standardization of genetics and environment, cost efficiency, and the possibility to introduce targeted genetic modifications for the generation of tailored disease models. However, due to differences in anatomical and physiological characteristics, rodent models do not always reflect the situation of human patients sufficiently well to be predictive in terms of efficacy and safety of new therapies. In this respect, the pig has been discussed as a missing link between mouse models and human patients. As a monogastric omnivore, the pig shares many anatomical and physiological similarities with humans. Importantly, the techniques for genetic modification of pigs have been refined to a level allowing almost the same spectrum of alterations as in mouse models (Aigner et al. 2010 J. Mol. Med. (Berl.) 88, 653–664). These include inducible transgene expression systems (Klymiuk et al. 2012 FASEB J. 26, 1086–1099) as well as the introduction of targeted genetic modifications (Klymiuk et al. 2012 J. Mol. Med. (Berl.) 90, 597–608). A major focus of our laboratory is the generation, characterisation, and implementation of pig models for translational diabetes research. Transgenic pigs expressing a dominant negative receptor for the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) demonstrated a crucial role of the GIP system for the physiological age-related expansion of pancreatic β-cell mass. Moreover, this animal model shares important characteristics of type 2 diabetes mellitus: impaired incretin effect, reduced glucose tolerance and insulin secretion, and a progressive reduction of β-cell mass (Renner et al. 2010 Diabetes 59, 1228–1238). More recently, we used this model to search for metabolic biomarkers which are associated with progression in the pre-diabetic period and identified specific amino acid and lipid signatures as candidate biomarkers (Renner et al. 2012 Diabetes 61, 2166–2175). Further, we created the first pig model for permanent neonatal diabetes by expression C94Y mutant insulin in the β-cells of transgenic pigs. In addition to their use as biomedical models, pigs may also serve as organ and tissue donors for xenotransplantation. Transplantation of encapsulated porcine pancreatic islets to type 1 diabetic patients with severe unaware hypoglycemia has already entered clinical studies, but encapsulation may shorten the lifespan of the islets. Therefore, in order to overcome the rejection of pig islets by human T-cells, we generated transgenic pigs expressing the optimized CTLA-4Ig variant LEA29Y in the pancreatic β-cells. Islets from LEA29Y transgenic pigs rescued diabetes and were protected against rejection in a humanized mouse model (Klymiuk et al. 2012 Diabetes 61, 1527–1532).
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Franco, Nuno Henrique, Sonia Batista Miranda, Nóra Kovács, Attila Nagy, Bùi Quốc Thiện, Flávio Reis, and Orsolya Varga. "Assessing Scientific Soundness and Translational Value of Animal Studies on DPP4 Inhibitors for Treating Type 2 Diabetes Mellitus." Biology 10, no. 2 (February 16, 2021): 155. http://dx.doi.org/10.3390/biology10020155.
Full textAbstract:
Although there is a wide range of animal models of type 2 diabetes mellitus (T2DM) used in research; we have limited evidence on their translation value. This paper provides a) a comparison of preclinical animal and clinical results on the effect of five dipeptidyl peptidase-4 (DPP4) inhibitors by comparing the pharmaceutical caused glucose changes, and b) an evaluation of methodological and reporting standards in T2DM preclinical animal studies. DPP4 inhibitors play an important role in the clinical management of T2DM: if metformin alone is not sufficient enough to control the blood sugar levels, DPP4 inhibitors are often used as second-line therapy; additionally, DPP-4 inhibitors are also used in triple therapies with metformin and sodium-glucose co-transporter-2 (SGLT-2) inhibitors or with metformin and insulin. In our analysis of 124 preclinical studies and 47 clinical trials, (1) we found no evidence of species differences in glucose change response to DPP4 inhibitors, which may suggest that, for this drug class, studies in mice and rats may be equally predictive of how well a drug will work in humans; and (2) there is good reporting of group size, sex, age, euthanasia method and self-reported compliance with animal welfare regulations in animal studies but poor reporting of justification of group size, along with a strong bias towards the use of male animals and young animals. Instead of the common non-transparent model selection, we call for a reflective and evidenced-based assessment of predictive validity of the animal models currently available.
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Hira, Tohru, Aphichat Trakooncharoenvit, Hayate Taguchi, and Hiroshi Hara. "Improvement of Glucose Tolerance by Food Factors Having Glucagon-Like Peptide-1 Releasing Activity." International Journal of Molecular Sciences 22, no. 12 (June 21, 2021): 6623. http://dx.doi.org/10.3390/ijms22126623.
Full textAbstract:
Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone released from enteroendocrine L cells in response to meal ingestion. GLP-1 receptor agonists and GLP-1 enhancers have been clinically employed to treat diabetes owing to their glucose-dependent insulin-releasing activity. The release of GLP-1 is primarily stimulated by macronutrients such as glucose and fatty acids, which are nutritionally indispensable; however, excessive intake of sugar and fat is responsible for the development of obesity and diabetes. Therefore, GLP-1 releasing food factors, such as dietary peptides and non-nutrients, are deemed desirable for improving glucose tolerance. Human and animal studies have revealed that dietary proteins/peptides have a potent effect on stimulating GLP-1 secretion. Studies in enteroendocrine cell models have shown that dietary peptides, amino acids, and phytochemicals, such as quercetin, can directly stimulate GLP-1 secretion. In our animal experiments, these food factors improved glucose metabolism and increased GLP-1 secretion. Furthermore, some dietary peptides not only stimulated GLP-1 secretion but also reduced plasma peptidase activity, which is responsible for GLP-1 inactivation. Herein, we review the relationship between GLP-1 and food factors, especially dietary peptides and flavonoids. Accordingly, utilization of food factors with GLP-1-releasing/enhancing activity is a promising strategy for preventing and treating obesity and diabetes.
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Marszałek, Małgorzata. "Amylin under examination. Fibrillogenic potential of the troublesome molecule." Postępy Higieny i Medycyny Doświadczalnej 72 (April 16, 2018): 295–306. http://dx.doi.org/10.5604/01.3001.0011.7620.
Full textAbstract:
In patients or animals affected by 2 type diabetes mellitus (diabetes mellitus type 2 DM2, non-insulin dependent diabetes mellitus NIDDM) some pathological deposits, called amyloid are observed among cells of islets of Langerhans. Among others constituents deposits consist of insoluble, fibrillar form of polipeptide neurohormone called amylin, produced by pancreatic beta cells.. It is thought that formation of fibrillar deposits of misfolded and aggregated polipeptide is highly toxic to beta cells and leads to cell dysfunction, cell loss, pancreas destruction and progress of the disease. Due to the extreme insolubility of this polipeptide and its instant fibrillation amylin constitutes a methodological problem and there is a need for a special methodology in experiments. This article reviews the most important experiments aimed at discovering fibrillogenic potential of amylin and models of interaction of the polipeptide’s monomers in man and rat. Numerous methodological difficulties in amylin research has been also emphasized.
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Okamura, Tadashi, Xiang Yuan Pei, Ichiro Miyoshi, Yukiko Shimizu, Rieko Takanashi-Yanobu, Yasumasa Mototani, Takao Kanai, Jo Satoh, Noriko Kimura, and Noriyuki Kasai. "Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes." Journal of Diabetes Research 2013 (2013): 1–9. http://dx.doi.org/10.1155/2013/986462.
Full textAbstract:
Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA) rat derived from Long-Evans (LE) strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction ofβ-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus.
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Sener, A., I. Conget, J. Rasschaert, V. Leclercq-Meyer, M. L. Villanueva-Penacarrillo, I. Valverde, and W. J. Malaisse. "Insulinotropic action of glutamic acid dimethyl ester." American Journal of Physiology-Endocrinology and Metabolism 267, no. 4 (October 1, 1994): E573—E584. http://dx.doi.org/10.1152/ajpendo.1994.267.4.e573.
Full textAbstract:
Glutamic acid dimethyl ester (GME; 3.0–10.0 mM) enhanced insulin release evoked by 6.0–8.3 mM D-glucose, 1.0–10.0 mM L-leucine, or 5.0–10.0 mM 2-amino-bicyclo(2,2,1)heptane-2-carboxylic acid, causing a shift to the left of the sigmoidal relationship between insulin output and D-glucose concentration. In the absence of D-glucose, GME also unmasked the insulinotropic potential of glibenclamide. In islets exposed to L-leucine, the insulinotropic action of GME coincided with an early fall and later increase in 86Rb outflow and augmentation of 45Ca outflow from prelabeled islets. The measurement of O2 uptake, NH4+ output, production of 14CO2 from islets prelabeled with [U-14C]palmitate, generation of 14C-labeled amino acids and 14CO2 from the dimethyl ester of either L-[1-14C]glutamic acid or L-[U-14C]glutamic acid, and D-[2-14C]glucose as well as D-[6-14C]glucose oxidation in the presence or absence of GME indicated that the latter ester was efficiently converted to L-glutamate and its further metabolites. The overall gain in O2 uptake represented the balance between GME oxidation and its sparing action on the catabolism of endogenous fatty acids and exogenous D-glucose. It is proposed that GME might represent a new tool to bypass beta-cell defects in D-glucose transport, phosphorylation, and further metabolism and, hence, to stimulate insulin release in experiments conducted in animal models of non-insulin-dependent diabetes mellitus.
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Serik, S. A., and V. I. Strona. "Hypoglycemia and cardiac arrhythmias in diabetes mellitus." Ukrainian Therapeutical Journal, no. 3—4 (December 30, 2022): 69–79. http://dx.doi.org/10.30978/utj2022-3-69.
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The article provides an assessment of cardiovascular risks associated with episodes of hypoglycemia in patients with diabetes mellitus. The analysis has been performed for the experimental and clinical data on cardiac arrhythmias during induced hypoglycemia in animal models and in patients with diabetes. The pathogenetic mechanisms of the development of life‑threatening heart rhythm disorders during hypoglycemic states (in particular, changes in autonomic nervous system activation and in the serum level of potassium) have been considered. The nature of electrocardiographic changes preceding the development of arrhythmias during hypoglycemia is described and factors affecting QT interval duration during hypoglycemia are given. The authors highlight the results of clinical studies of spontaneous hypoglycemia in terms of the arrhythmias’ specific features in daytime and nocturnal hypoglycemia, and different mechanisms of the cardiac arrhythmias’ development at different periods of the day. Clinical data have been presented as regards the drug‑induced hypoglycemia during administration beta‑adrenergic receptor blockers, angiotensin‑converting enzyme inhibitors, fluoroquinolones, as well as mechanisms of dysglycemic effects of these drugs. It has been noted that β‑blockers can mask symptoms of catecholamine‑mediated hypoglycemia. It has been established that among hypoglycemic agents, insulin secretion stimulators (sulfonylureas, meglinides) and insulin have the highest risk of serious hypoglycemia. However, the use of basal and prandial insulin analogues was associated with a lower frequency of hypoglycemia compared to human insulin. It was emphasized that hypoglycemia should be avoided in clinical practice to improve prognosis and prevent arrhythmias. For this, it is necessary to individualize target glycemic values with their mitigation in high‑risk patients, to use the safest insulin and non‑insulin hypoglycemic agents, and to implement new technologies (pumps, continuous glucose monitoring) more widely. It is extremely important to take into account comorbidity and the effects on hypoglycemia risk of drugs used for the treatment of concomitant diseases.