Дисертації з теми "Diabetes resistance"
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1
Pickavance, Lucy Cecilia. "Thiazolidinedione treatment in models of insulin resistance." Thesis, University of Liverpool, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367553.
2
Ang, Christine W. M. "Diabetes and the maternal resistance vasculature." Thesis, University of Glasgow, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395080.
3
Hale, P. J. "Insulin resistance in diabetes mellitus and obesity." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.371516.
4
Eason, Robert C. "Treating type 2 diabetes through insulin resistance." Thesis, Aston University, 2002. http://publications.aston.ac.uk/10953/.
Анотація:
Type 2 diabetes is an insidious disorder, with micro and/or macrovascular and nervous damage occurring in many patients before diagnosis. This damage is caused by hyperglycaemia and the diverse effects of insulin resistance. Obesity, in particular central obesity, is a strong pre-disposing factor for type 2 diabetes. Skeletal muscle is the main site of insulin-stimulated glucose disposal and appears to be the first organ that becomes insulin resistant in the diabetic state, with later involvement of adipose tissue and the liver. This study has investigated the use of novel agents to ameliorate insulin-resistance in skeletal muscle as a means of identifying intervention sites against insulin resistance and of improving glucose uptake and metabolism by skeletal muscle. Glucose uptake was measured in vitro by cultured L6 myocytes and isolated muscles from normal and obese diabetic ob/ob mice, using either the tritiated non-metabolised glucose analogue 2-deoxy-D-glucose or by glucose disposal. Agents studied included lipoic acid, isoferulic acid, bradykinin, lipid mobilising factor (provisionally synonymous with Zinca2 glycoprotein) and the trace elements lithium, selenium and chromium. The putative role of TNFa in insulin resistance was also investigated. Lipoic acid improved insulin-stimulated glucose uptake in normal and insulin resistance murine muscles, as well as cultured myocytes. Isoferulic acid, bradykinin and LMF also produced a transient increase in glucose uptake in cultured myocytes. Physiological concentrations of TNFa were found to cause insulin resistance in cultured, but no in excised murine muscles. The effect of the M2 metabolite of the satiety-inducing agent sibutramine on lipolysis in excised murine and human adipocytes was also investigated. M2 increased lipolysis from normal lean and obese ob/ob mouse adipocytes. Arguably the most important observation was that M2 also increased the lipolytic rate in adipocytes from catecholamine resistant obese subjects. The studies reported in this thesis indicate that a diversity of agents can improve glucose uptake and ameliorate insulin resistance. It is likely that these agents are acting via different pathways. This thesis has also shown that M2 can induce lipolysis in both rodent and human adipocytes. M2 hence has potential to directly reduce adiposity, in addition to well documented effects via the central nervous system.
5
Reali, Federico. "Dynamical models for diabetes: insights into insulin resistance and type 1 diabetes." Doctoral thesis, Università degli studi di Trento, 2017. https://hdl.handle.net/11572/369184.
Анотація:
This thesis summarizes my work in systems biology as a PhD student at The Microsoft Research - University of Trento Centre for Computational and Systems Biology (COSBI) and at the University of Trento, department of Mathematics.
Systems biology is an interdisciplinary field that aims at integrating biology with computational and mathematical methods to gain a better understanding of biological phenomena [5, 6]. Among these methods, mathematical and dy- namical modeling have driven the discovery of mechanistic insights from the static representations of phenomena, that is, data. As a result, mathematical and dynamical models have now become standard tools to support new discoveries in biology and in public health issues. For example, models assist governments in determining the policies to contain the spreading of the diseases and in decisions such as vaccine purchases [7]. Similarly, complex and accurate models of the cardio-vascular systems guide surgeons during many procedures on pa- tients [8]. Furthermore, dynamical models of signaling cascades help researchers in identifying new potential drug targets and therapies for many diseases [9]. We used these modeling techniques to address biological questions related to diabetes and insulin resistance. Within this framework, this thesis contains two articles I contributed to, that focus on diabetes. These works are published in the journal of Nature Scientific Reports and are included in Chapters 3 and 4.
A significant contribution to the development of these models, and models in general, is given by optimization. Optimization is often used in modeling to determine certain unknown values or factors in a way that allow the model to optimally reproduce the experimental data. Moreover, the parameters of a model that correctly describe the undergoing dynamics may be used as diagnostic tools [10–13]. To this end, this thesis contains a methodological appendix that includes a review of optimization algorithms that has been submitted to the journal of Frontiers in Applied Mathematics and Statistics, special topic Optimization. The content of this article is reported in Appendix A.
6
Reali, Federico. "Dynamical models for diabetes: insights into insulin resistance and type 1 diabetes." Doctoral thesis, University of Trento, 2017. http://eprints-phd.biblio.unitn.it/1962/1/Reali_PhDThesis.pdf.
Анотація:
This thesis summarizes my work in systems biology as a PhD student at The Microsoft Research - University of Trento Centre for Computational and Systems Biology (COSBI) and at the University of Trento, department of Mathematics.
Systems biology is an interdisciplinary field that aims at integrating biology with computational and mathematical methods to gain a better understanding of biological phenomena [5, 6]. Among these methods, mathematical and dy- namical modeling have driven the discovery of mechanistic insights from the static representations of phenomena, that is, data. As a result, mathematical and dynamical models have now become standard tools to support new discoveries in biology and in public health issues. For example, models assist governments in determining the policies to contain the spreading of the diseases and in decisions such as vaccine purchases [7]. Similarly, complex and accurate models of the cardio-vascular systems guide surgeons during many procedures on pa- tients [8]. Furthermore, dynamical models of signaling cascades help researchers in identifying new potential drug targets and therapies for many diseases [9]. We used these modeling techniques to address biological questions related to diabetes and insulin resistance. Within this framework, this thesis contains two articles I contributed to, that focus on diabetes. These works are published in the journal of Nature Scientific Reports and are included in Chapters 3 and 4.
A significant contribution to the development of these models, and models in general, is given by optimization. Optimization is often used in modeling to determine certain unknown values or factors in a way that allow the model to optimally reproduce the experimental data. Moreover, the parameters of a model that correctly describe the undergoing dynamics may be used as diagnostic tools [10–13]. To this end, this thesis contains a methodological appendix that includes a review of optimization algorithms that has been submitted to the journal of Frontiers in Applied Mathematics and Statistics, special topic Optimization. The content of this article is reported in Appendix A.
7
Lindmark, Stina. "Neurohormonal mechanisms in insulin resistance and type 2 diabetes." Doctoral thesis, Umeå : Univ, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-225.
8
Hunter, Steven J. "Insulin resistance : underlying mechanisms and influence of treatment." Thesis, Queen's University Belfast, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337044.
9
Relton, Caroline L. "The identification and characterisation of genes associated with insulin resistance." Thesis, University of Newcastle Upon Tyne, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.264425.
10
Vella, Sandro. "Pharmacological modulation of insulin resistance : benefits and harms." Thesis, University of Dundee, 2013. https://discovery.dundee.ac.uk/en/studentTheses/4428eca5-5018-4816-95d0-30c0a3043409.
Анотація:
Aims: Thiazolidinediones have been advocated as second or third line insulin sensitizing agents in the management of type 2 diabetes (T2DM). Their widespread use has been hampered by concerns about their cardiovascular safety, including fluid retention. Metformin is established as first-line glucose-lowering pharmacotherapy in T2DM. It has also been suggested that it may have benefits in alleviating insulin resistance in type 1 diabetes (T1DM). This thesis examined: (i) cardiovascular, renal and metabolic differences between individuals with T2DM ‘tolerant’ or ‘intolerant’ of TZDs; (ii) risk factors for TZD-associated oedema in T2DM; and (iii) the potential for metformin as adjunct therapy in T1DM. Methods: (i) A small clinical study characterising TZD tolerant and intolerant individuals with T2DM; (ii) A population-based epidemiological study of TZD induced oedema in individuals with T2DM in Tayside, Scotland (using incident loop diuretic prescription as a surrogate); (iii) A systematic review and meta-analysis of published studies of adjunct metformin in T1DM. Results (i) During a five-day high sodium diet, two known TZD-intolerant individuals with T2DM had reductions in haematocrit, aldosterone, and diastolic BP and increases in ANP and central and peripheral augmentation indices which were outwith reference ranges derived from nine TZD-tolerant individuals; (ii) Predictors of time to loop diuretic prescription included age, body mass index, systolic BP, haematocrit, ALT and macrovascular disease but rates of this outcome did not differ by therapy: 4.3% (TZDs) vs 4.7% (other agents) [unadjusted OR 0.909 (95% CI 0.690, 1.196); p = 0.493]; (iii) In meta-analysis of nine small studies in T1DM (192.8 patient-years of follow-up), metformin was associated with a reduction in total daily insulin dose (6.6 units/day; p < 0.001) but no studies examined cardiovascular surrogates or outcomes. Conclusions: Hypotheses were generated for several potential biomarkers predictive of TZD-induced oedema but the clinical importance of TZDs as a risk factor for oedema in individuals with T2DM was questioned. As there is some evidence for the safety of metformin as an adjunct therapy in T1DM but little evidence of efficacy, larger studies are warranted.
11
Lee, Katie Ting Yan. "Novel wild-derived mouse models of obesity and diabetes resistance." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/41985.
Анотація:
Novel inbred mouse strains have been developed from wild-caught mice, and they display enhanced genetic diversity compared to the commonly used strains. We hypothesized that their unique genotypes may yield aspects of disease susceptibility previously unobserved in the commonly used strains. We examined two of these strains, PWD/PhJ (PWD) and WSB/EiJ (WSB), for obesity and type 2 diabetes (T2D)-related traits in response to high fat diet (HFD) feeding and compared them to the C57BL/6J (B6) strain. We identified PWD mice as a model of primary hyperinsulinemia. They had increased insulin levels at a young age while they were lean and insulin sensitive. They were protected from early development of diet-induced obesity, although they later developed obesity similar to B6 mice that may be induced by chronic hyperinsulinemia. PWD mice are a novel model of primary hyperinsulinemia as a cause of obesity. WSB mice are a model of extraordinary resistance to HFD-associated obesity and T2D. They have a higher energy expenditure that may have contributed to their protection from HFD-induced obesity. PWD and WSB mice modeled novel aspects of disease susceptibility and are interesting models for further study to determine the mechanisms associated with the pathogenesis of obesity and T2D.
12
Marakis, Georgios. "Natural therapy for insulin-resistance syndrome and type II diabetes." Thesis, University of Reading, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340013.
13
Järvi, Anette. "Carbohydrate-rich foods in the treatment of the insulin resistance syndrome : studies of the importance of the glycaemic index and dietary fibre /." Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-5166-7/.
14
Clarke, Stephen. "Liver steatosis and insulin-resistance : reversal by Sutherlandia frutescens." Thesis, Nelson Mandela Metropolitan University, 2014. http://hdl.handle.net/10948/d1020788.
Анотація:
Type 2 diabetes mellitus (T2DM) is rapidly emerging as one of the greatest global health issues of the 21st century. Insulin-resistance is a condition associated with T2DM and in the cell it is defined as the inadequate strength of insulin signalling from the insulin receptor downstream to the final substrates of insulin action involved in multiple metabolic, gene expression, and mitogenic aspects of cellular function. To investigate the potential mechanisms involved in the development of insulin-resistance, two in vitro liver cell models were established using palmitate or a combination of insulin and fructose as inducers. The development of insulin-resistance was determined via the capacity of the hepatocytes to maintain normal glucose metabolism functionality by measuring hepatic gluconeogenesis and glycogenolysis. It was established that the treatments induced the development of insulinresistance after 24 hours chronic exposure. Previous studies have investigated the potential of Sutherlandia frutescens extracts as therapeutic agents for insulin-resistance. The aim of this study was thus to investigate the ability of a hot aqueous extract of S. frutescens to reverse the insulin-resistant state, via measuring gluconeogenesis and glycogenolysis, the associated changes in cellular physiology (lipid accumulation, oxidative stress, and acetyl- CoA levels), and changes in mRNA expression. The results showed that S. frutescens had a significant effect on reversing the insulin-resistant state in both models of insulin-resistance. Furthermore, S. frutescens was capable of reducing lipid accumulation in the form of triacylglycerol in the high insulin/fructose model, while this was unaffected in the palmitate model. However, S. frutescens did reduce the accumulation of diacylglycerol in the palmitate model. Oxidative stress, seen to be associated with the insulin-resistant state, was successfully treated using the extract, as indicated by a reduction in reactive oxygen species. However no change was seen in the nitric oxide levels, in either model. Interestingly, although S. frutescens had no effect on the level of acetyl-CoA in the insulin/fructose model, it was found to increase this in the palmitate model. It is suggested that this may be due to increased β-oxidation and metabolic activity induced by the extract. The analysis of mRNA expression gave some insight into possible mechanisms by which insulin-resistance develops, although the results were inconclusive due to high variability in samples and the possibility of the RNA being compromised. Future studies will address this issue. The results of this study reflect different proposed clinical causes of insulin-resistance through the responses seen in the two cell models. These indicate that liver steatosis and insulin-resistance are induced by high palmitate as well as high insulin and fructose levels, and reversed by S. frutescens. Therefore the potential of S. frutescens to be used as a therapeutic agent in the treatment of insulin-resistance is indicated by this study.
15
Phillips, Amanda S. "The Influence of Perceived Stress on Insulin Resistance in Adults with Type 2 Diabetes." Thesis, University of North Texas, 2014. https://digital.library.unt.edu/ark:/67531/metadc699935/.
Анотація:
Objective: To identify whether perceived stress is a risk-factor for higher cortisol levels and greater insulin resistance in Type 2 diabetic patients, using data from participants with and without diabetes in the National Survey of Midlife Development in the United States (MIDUS), specifically MIDUS II, Project 4. The following hypotheses were tested: (H1a) greater perceived stress would be associated with higher cortisol for Type 2 diabetic participants, (H1b) the perceived stress/cortisol relationship would be stronger for people with Type 2 diabetes than for those without it, (H2) greater perceived stress would be associated with higher Homeostatic Model Assessment-Insulin Resistance (HOMA-IR, insulin-resistance) for Type 2 diabetic participants, (H3a) subjective well-being would moderate the perceived stress/insulin resistance relationship for Type 2 diabetic participants, and (H3b) depression would moderate the perceived stress/insulin resistance relationship for Type 2 diabetic participants. Method: MIDUS, a longitudinal study of over 7,000 American adults, explores biopsychosocial factors that could contribute to variance in mental/physical health. Only complete data were utilized. Type 2 participants (n=115) consisted of 54 males and 62 females ranging in age from 36 to 81 years. Non-diabetic participants (n=1097) consisted of 470 males and 627 females ranging in age from 34 to 84 years. Results: None of the predicted relationships were statistically significant. Waist to hip ratio was significantly related to insulin resistance (r = .31, p = .001). Conclusions: Future studies should collect information about the type and duration of stressors in addition to perceptions about stress for those with Type 2 diabetes.
16
Kershner, David. "Oral Glucose Insulin Secretion Test for Identifying Patients with Insulin Resistance." ScholarWorks, 2018. https://scholarworks.waldenu.edu/dissertations/5634.
Анотація:
Insulin resistance is an increasing public health issue with the current literature, suggesting reduced sensitivity of insulin leads to adult onset diabetes and associated downstream pathologies that reduce life expectancy. The main objectives of this study were to evaluate the ability of the Oral Glucose Insulin Secretion Test (OGIST) to identify insulin resistance and examine differences in the insulin sensitivity based on gender, age, and ethnicity. This study was supported by the insulin resistance theory which focuses on the reduced ability of insulin to bind to the cellular insulin receptor, reducing the sensitivity of insulin. The OGIST lab results of a total of 250 patients, aged 18-65, were included in this study from a major city in the midwestern United States. Binomial logistic regression was used to evaluate the relationship between the dependent variables and the validation independent variables and analyze the possible differences seen in insulin, proinsulin, C-peptide, and HbA1c with age. The OGIST demonstrated the ability to identify elevated levels of insulin, proinsulin, and C-peptide at the end of the first phase insulin secretion to glucose. The results of this study demonstrated patients with insulin resistance exhibited a greater reduction in insulin production with age compared to those without insulin resistance. There were no changes observed between gender or ethnicity. The OGIST was the only test that demonstrated the ability to identify the individual's insulin sensitivity, β-cell function, and progression to diabetes. The ability of the OGIST to identify both insulin resistance and β-cell function can contribute to positive social change by encouraging further research for the early diagnosis and treatment of insulin resistance and the reduction in adult onset diabetes.
17
Bagstaff, Stephanie M. "Hyperinsulinemia and insulin resistance in cultured human muscle cells." Thesis, University of Newcastle Upon Tyne, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270177.
18
Gelcich, Sarah. "Exploring risk, resistance and closing talk in chronic diabetes routine consultations." Thesis, University of Sheffield, 2017. http://etheses.whiterose.ac.uk/19167/.
Анотація:
Qualitative research is widely recognised as making a valuable contribution to healthcare practice and policy. One area of study that has noticeably relied on qualitative research is doctor-patient communication, due to the fact that practitioner-patient interaction is inherently dependent on talk. One methodology that has proven very useful in order to analyse practitioner-patient interaction is Conversation Analysis (CA). Little seems to have been done in terms of analysing practitioner-patient talk within chronic routine consultations. Routine consultations are especially important in the treatment of long-term conditions such as type 2 diabetes. This study analyses the talk between type 2 diabetic patients and a practice nurse during their routine consultations. The study will address four main points. Firstly, it will determine the differences between diabetic chronic routine consultations and acute primary care visits. Secondly, based on these differences, it will address the closing phase of these visits. Thirdly, it will establish how communication of risk takes place during these consultations and lastly it will demonstrate how disagreement takes place during these visits. Analysing these elements within chronic routine consultations can potentially inform best practice when it comes to closing a visit, communicating risk and identifying patient disagreement. The analysis and presentation of significant differences between chronic and acute visits could have an effect on patients presenting new concerns and in turn could affect their long-term care.
19
Fryer, Lee George Daniel. "Studies into the role of glucose transporter function in insulin resistance." Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265007.
20
Crawford, Lynne Mary. "The regulation of triglyceride metabolism in the liver and adipose tissue." Thesis, University of Glasgow, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263457.
21
Ranasinghe, Dilip Chathuranga. "The effects of supervised aerobic and resistance exercise training on Sri Lankan adults with type 2 diabetes mellitus: Sri Lanka diabetes aerobic and resistance training (SL-DART) study." Thesis, Queensland University of Technology, 2018. https://eprints.qut.edu.au/115457/1/115457_9304177_ranasinghe_dilip_chathuranga_thesis.pdf.
Анотація:
This study had 2 components investigating the effects of exercise in Sri Lankan adults with type 2 diabetes mellitus (T2DM). The quantitative component consisted of a 12 week randomized controlled trial comparing aerobic training, resistance training and usual care on glycaemic control (HBA1C), % body fat and range of clinically important endpoints. The qualitative component consisted of in-depth interviews to determine barriers/facilitators for adherence to different modes of exercise. The study proved, despite cultural challenges and barriers, the possibility of conducting a large-scale exercise intervention in Sri Lankans for the first time and merit of exercise in Sri Lankans with T2DM.
22
Andrews, Tara Jane. "The role of endothelial function and oxidant stress in a model of insulin resistance." Thesis, Queen Mary, University of London, 2003. http://qmro.qmul.ac.uk/xmlui/handle/123456789/28587.
Анотація:
Type 2 diabetes mellitus affects over 100 million people worldwide. It is characterized by various metabolic abnormalities such as insulin resistance, aberrant insulin secretion, hyperglycaemia and a cluster of cardiovascular risk factors, including increased oxidative stress. It is associated with microvascular complications and increased potential of macrovascular disease. The aim of the studies described in this thesis was to test the hypothesis that oxidant stress contributes to an altered vascular function and impaired insulin regulation in a pre-diabetic animal model- the obese Zucker rats. The first objective was to develop new methods to measure endothelial function in animal disease models. Firstly, without autonomic control - the in situ perfused hindquarters, and secondly, with autonomic control - the in vivo Doppler ear blood flow. The obese Zucker rat was shown to have increased oxidative stress, as measured by plasma 8-epi-PGF2a,. It also had high insulin and glucose levels and impaired glucose disposal. Obese rats also had increased agonist-induced nitric oxide-dependent endothelial responses; these were further enhanced by insulin in a macrovascular preparation, but were impaired by insulin in a resistance vessel bed. Following dietary treatment with the antioxidants, the obese plasma insulin/glucose ratio was improved. However, vitamin E blunted the enhanced endothelial-dependent vasodilator responses, and decreased plasma levels of 8-epi-PGF2a. In contrast, pro-oxidant treatment with hydroquinone and buthionine-sulphoximine impaired the plasma insulin/glucose ratio, abolished endothelial hyperactivity but increased plasma 8-epi-PGF2a levels. Interestingly, fructose protected against pro-oxidant-induced increases in plasma 8-epi-PGF2a levels and further increases in glucose-induced plasma insulin. In summary the redox status in obese Zucker rats was modified with antioxidant and prooxidant treatment. This resulted in compensatory changes in glucose disposal and endothelial function. Impaired endothelial function may initiate "damage" especially in those individuals susceptible to syndrome X, leading to insulin insensitivity and vascular dysfunction in type 2 diabetes.
23
McClean, Paula. "Inhibition of GIP signalling alleviates obesity, insulin resistance and type 2 diabetes." Thesis, University of Ulster, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494369.
24
Wiggam, Malcolm Ivan. "Aspects of insulin resistance in essential hypertension and insulin-dependent diabetes mellitus." Thesis, Queen's University Belfast, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387971.
25
Cairncross, Joy Claudia. "The effect of 14 weeks of strength training on insulin resistance." Thesis, Nelson Mandela Metropolitan University, 2013. http://hdl.handle.net/10948/d1018276.
Анотація:
Insulin resistance is a precursor to type II diabetes mellitus and in conjunction with dyslipidaemia, hypertension, and obesity, these abnormalities constitute the metabolic syndrome. Insulin resistance usually develops before these other diseases and therefore identifying and successfully treating insulin resistant patients may have potentially great preventive value. Insulin resistance, obesity, and subsequently type II diabetes mellitus have increased dramatically and have reached epidemic proportions. The incidence of diabetes, and in particular type II diabetes mellitus, is increasing in developing countries and throughout the world and this is mainly as a result of increasingly sedentary lifestyle and obesity in an aging population. The specific aim of this study was to explore and describe the effect of a 14-week strength-based resistance training programme on insulin resistance amongst individuals aged 25 to 68 years, who are pre-diabetic, have T2DM, and/or are overweight. The research approach used in this investigation was explorative, experimental, and quantitative in nature. The quasi-experimental design consisted of a pre-test and post-test for an experimental and comparison group who were chosen through convenience and snowball sampling. A total of 30 participants were involved in this study, 15 participants in each group. The following dependent variables were selected, namely: body weight; BMI; body composition; waist-to-hip ratio; total cholesterol levels; triglyceride levels; HOMA-IR; and muscle strength for upper and lower body. Pre-and post-test analysis was performed at the Biokinetics and Sport Science Unit, located at the Nelson Mandela Metropolitan University (NMMU). Blood samples of the participants were drawn by nurses at the Health Clinic at the Nelson Mandela Metropolitan University and these blood plasma samples were stored at the Department of Microbiology and Biochemistry at NMMU for later analysis of glucose and insulin. The experimental group trained three times per week for a period of fourteen weeks, performing strength training exercises with progressive increments in the intensity of the exercise. The control group remained sedentary throughout the intervention period. Analysis of the data was conducted utilizing descriptive and inferential statistics. Analysis of variance (ANOVA) was used as a hypothesis-testing procedure to evaluate the mean differences. The following dependent variables showed a decrease in mean values: body weight, body mass index, body fat percentage, waist minimum, cholesterol and insulin. However these differences in results were not practically and statistically significant. The following dependent variables showed an increase in mean values: hip maximum, arm relaxed, arm flexed, thigh circumference, glucose and HOMA-IR. However these results were not practically and statistically significant. The mean differences in the plasma insulin level, pre- to post-test, between both groups indicated that a significant difference (t = -1.77, p = 0.044) existed between them. Cohen‟s d revealed a value of 0.64, which indicates moderate practical significance. The only dependent variable which showed both statistical and practical significance was sum of skinfolds. The findings for sum of skinfolds revealed that the mean differences, from pre- to post-test, between both groups indicated that a significant difference (t = -2.30, p = 0.015) existed between them. Cohen‟s d revealed a value of 0.84, which indicated a large practical significance. Although the sample size was too small to indicate generalisations to the diabetic population as a whole, strength training should be furthermore explored as an alternative and successful modality in the existing range of options available to the health and exercise professional to address the needs of the person with T2DM. The researcher proposed that a bigger sample size be used for the experimental and control group, the intervention period increased as well as various differences related to frequency, intensity and duration of strength training could possibly result in significant changes.
26
Jun, Lucy Soo Yon. "Thyroid hormone-regulated skeletal muscle Glut4 glucose transporter trafficking during fasting in diet-induced obesity and insulin resistance." CSUSB ScholarWorks, 2005. https://scholarworks.lib.csusb.edu/etd-project/2869.
Анотація:
This thesis project will investigate the effects of fasting on the serum levels of two key regulatory hormones, insulin and thyroid hormone (T3) and the effects of these hormones on the trafficking of Glut4 on soleus muscle.
27
Kuhl, Jeanette. "Pathogenesis of type 2 diabetes with emphasis on the mechanism of insulin resistance /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-839-8/.
28
Stone, Monique Lee Women's & Children's Health Faculty of Medicine UNSW. "Poor glycaemic control in adolescents with type 1 diabetes." Publisher:University of New South Wales. Women's & Children's Health, 2008. http://handle.unsw.edu.au/1959.4/41281.
Анотація:
Many adolescents with type 1 diabetes (T1DM) have suboptimal glycaemic control, increasing the risk of diabetic complications. This thesis explores some of the causes, consequences and therapeutic options for adolescents with T1DM and poor glycaemic control. Insulin resistance occurs in T1DM and normal puberty and contributes to poor glycaemic control. The effect of rosiglitazone, an insulin sensitizer, in addition to insulin on the glycaemic control of adolescents with T1DM was tested using a randomized, double blind placebo controlled trial. Treatment with rosiglitazone did not improve HbA1c, however there was a significant reduction in insulin dose and adiponectin, suggesting improved in insulin sensitivity. Insulin sensitivity by euglycaemic hyperinsulinaemic clamp varied widely between individuals and there was no consistent pattern with rosiglitazone. Potential markers of insulin resistance in T1DM were examined. Total and high molecular weight (HMW) adiponectin levels were lower in children and adolescents with T1DM than controls. HMW adiponectin was significantly associated with other markers of insulin resistance, such as insulin dose, body mass index standard deviation score (BMI-SDS), age, pubertal stage and duration of diabetes. There is increasing evidence that insulin resistance may play a role in T1DM complications. The natural history and risk factors for the development of microalbuminuria was described using a retrospective cohort study of 972 children and adolescents. Most cases of microalbuminuria were transient. Apart from baseline albumin excretion rate, HbA1c and age at diagnosis, other predictors of subsequently developing persistent microalbuminuria included several markers of insulin resistance (higher cholesterol, BMI-SDS, and insulin dose). In addition to insulin resistance, there are many other factors that contribute to glycaemic control. The role of the variability in carbohydrate intake was assessed using questionnaires and food diaries. Although carbohydrate consumption varied by approximately 45grams each day, it had no significant correlation with HbA1c. The impact of socioeconomic status, quality of life and health care delivery is discussed by comparing glycaemic control of children with T1DM in three diabetes centres. A model for the factors associated with poor glycaemic control in adolescents with T1DM is proposed, and the challenges of research and clinical practice in this population are discussed.
29
Erickson, Andrea Rose. "The Association Between Dairy Consumption and Insulin Resistance." BYU ScholarsArchive, 2013. https://scholarsarchive.byu.edu/etd/4262.
Анотація:
Background: A cross-sectional design was employed to ascertain the relationship between dairy consumption and insulin resistance (IR) in 272 middle-aged, nondiabetic women. Methods: Participants kept a seven-day weighed food record to report their diets, including consumption of dairy foods. IR was assessed using the homeostatic model assessment (HOMA), using the following formula: fasting plasma insulin (µU/ml) x fasting plasma glucose (mg/dL)/405. The Bod Pod was used to examine body fat percentage, and accelerometry over a seven-day period was used to assess physical activity. HOMA values were log-transformed and regression analysis and the General Linear Model procedure were used to determine how mean HOMA differed across low, moderate, and high dairy intake groups. Results: (Mean ± SD) age: 40.1 ± 3.0 years, physical activity (average activity counts for one week, divided by 1,000): 2700.1 ± 781.9, body fat percentage: 31.7 ± 6.9, weight (kg): 66.1 ± 10.0, fasting glucose (mg/dL): 86.7 ± 5.9, fasting insulin (µU/mL): 7.0 ± 4.2, energy intake (kcal/day): 2051.9 ± 319.1, kcal from carbohydrate (%): 55.7 ± 6.2, kcal from protein (%): 13.8 ± 2.5, kcal from fat (%): 30.5 ± 5.8, soluble fiber (g per 1,000 kcal): 1.7 ± 0.9, insoluble fiber (g per 1,000 kcal): 3.8 ± 1.9, dairy intake (servings/day): 1.1 ± 1.0, HOMA: 1.5 ± 1.0, log-transformed HOMA: 0.3 ± 0.6. Those in the highest quartile for dairy consumption had significantly higher log-transformed HOMA (0.41 ± 0.53) than those in the moderate (0.22 ± 0.55) or low (0.19 ± 0.58) consumption categories (F = 6.90, p = 0.0091). This relationship remained significant after controlling for all covariates (F = 4.71, p = 0.030). Controlling for physical activity strengthened the relationship between dairy consumption and IR by 7%. Adjusting for body weight, percent of kcal from fat, and insoluble and soluble fiber intake also strengthened the relationship. Controlling for energy intake and body fat percentage weakened the relationship by 32% and 13%, respectively, though it remained significant. Conclusion: High dairy consumption is significantly associated with IR in middle-aged, nondiabetic women.
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Winnick, Jason Joseph. "Effect of aerobic exercise on peripheral glucose uptake and endogenous glucose production in type 2 diabetes mellitus." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1157551296.
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Ng, Foong Loo Yvonne Biotechnology & Biomolecular Sciences Faculty of Science UNSW. "Insulin action: unravelling AKT signalling in Adipocytes." Awarded by:University of New South Wales. Biotechnology & Biomolecular Sciences, 2009. http://handle.unsw.edu.au/1959.4/44628.
Анотація:
The Ser/Thr kinase Akt plays an important role in many of insulin's actions including GLUT4 translocation to the plasma membrane (PM). However, there are several features of Akt's regulation of GLUT4 translocation that remain unclear. The goal of my thesis was to resolve some of the following questions: Is activation of Akt sufficient to stimulate GLUT4 translocation? What is the quantitative relationship in signal transmission between individual components within the Akt cascade? What is the role of Akt in insulin resistance? To determine if activation of Akt is sufficient to mediate GLUT4 translocation, I developed a drug-inducible heterodimerisation strategy to activate Akt2 independently of other potential insulin signalling pathways. These studies revealed that activation of Akt2 resulted in rapid stimulation of GLUT4 translocation to a similar extent with maximum insulin, indicating that Akt2 is sufficient for this event. It was previously observed that maximum effect of insulin on GLUT4 translocation was obtained with minimum activation of Akt. To resolve this discrepancy, the relationship between Akt signalling components was examined using a quantitative kinetic and dose response approach combined with hierarchical cluster analysis. Most notably I observed a strong relationship between Akt at the PM, but not Akt in the whole cell lysate, with its substrate phosphorylation. Active pools of phospho-Akt and -AS160, a major substrate involved in GLUT4 translocation, were found in the lipid raft, highlighting the importance of subcellular partitioning of key signalling components for achieving biological specificity. The involvement of Akt in insulin resistance was investigated using the heterodimerisation strategy. These studies revealed that insulin itself initiates a pathway that causes insulin resistance by converging on target(s) downstream of Akt. This inhibitory pathway emanates from PI3-kinase and is likely induced by a range of insults including chronic insulin and dexamethasone. In conclusion, Akt is a crucial element in the insulin action pathway that exhibits precise spatial regulation. While the role of this nanoregulation of Akt in disease remains to be evaluated, my studies suggest that the major defect contributing to insulin resistance occurs downstream of Akt. The elucidation of this target will have major implications for metabolic diseases.
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Moncrieft, Ashley E. "Inactivity, Inflammation, and Insulin Resistance in Type 2 Diabetes and the Metabolic Syndrome." Scholarly Repository, 2011. http://scholarlyrepository.miami.edu/oa_theses/300.
Анотація:
Both type 2 diabetes (T2D) and the the metabolic syndrome (MetS) have been shown to increase the risk of cardiovascular disease (CVD). Inflammation and insulin resistance have each been associated with the development of MetS and the onset of T2D as well as the risk of CVD. Inflammation and insulin resistance are therefore suitable targets for public health initiatives and interventions in persons at risk for or living with CVD. Physical inactivity is a major risk factor for CVD as well as MetS and T2D. Conversely, increased physical activity is associated with improved health outcomes for individuals with a high risk for developing CVD. Two possible mechanisms for the deleterious effects of inactivity on health are inflammation and insulin resistance. Researchers have hypothesized that increased adiposity and reduced fitness are partially responsible for the associations between inactivity, inflammation, and insulin resistance. However, these relationships have not been studied extensively in overweight/obese individuals, who are often unfit and sedentary. The purpose of this study was to further examine the relationship between baseline measures of walking activity and sedentary behavior, and inflammation and insulin resistance in a sample of adults with type 2 diabetes and/or metabolic syndrome. This thesis examined baseline data from participants enrolled in either of two studies of patients with T2D (n = 116) or MetS without T2D (n = 126). Participants included low income men and women (not pregnant or nursing) between the ages of 18 and 70 who either show depressed affect (BDI > 11), and were overweight (BMI ≥ 27 kg/m2) and had type 2 diabetes or had at least 3 components of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) classification of the metabolic syndrome (MetS). Structural equation modeling was used to determine if physical inactivity is associated with inflammation or insulin resistance in these conditions. Possible mediational roles of adiposity and low cardiorespiratory fitness were also examined. Additional analyses were conducted to determine if these relationships can be estimated equally in MetS and T2D conditions. Activity was indirectly related to abdominal adiposity via an indirect, positive association with cardiorespiratory fitness. Abdominal adiposity was positively related to both inflammation and insulin resistance. There were no direct associations between activity and inflammation or insulin resistance in this population. Therefore, walking may be negatively related to cardiovascular risk, insofar as it reduces abdominal adiposity.
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Song, Xiao Mei. "Insulin signal transduction in skeletal muscle : special consideration for insulin resistance and diabetes /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4502-0/.
34
Danielsson, Anna. "Insulin signalling in human adipocytes : mechanisms of insulin resistance in type 2 diabetes." Doctoral thesis, Linköping : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-10327.
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Puthanveetil, Prasanth Nair. "Role of cardiac FoxO1 in conditions of insulin resistance, nutrient excess, and diabetes." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/41051.
Анотація:
Glucocorticoids increase PDK4 mRNA and protein expression, which phosphorylates PDH, thereby preventing the formed pyruvate from undergoing mitochondrial oxidation. This increase in PDK4 expression is mediated by the mandatory presence of FoxOs in the nucleus. Rat cardiomyocytes exposed to Dx produced a robust decrease in glucose oxidation. Measurement of FoxO compartmentalization demonstrated increase in nuclear, but resultant decrease in cytosolic content of FoxO1 with no change in the total content. The increase in nuclear content of FoxO1 correlated to an increase in nuclear phospho p38 MAPK together with a robust association between this transcription factor and kinase. Dx also promoted nuclear retention of FoxO1 through a decrease in phosphorylation of Akt, an effect mediated by heat shock proteins binding to Akt. Instead, Dx increased the association of Sirt1 with FoxO1, thereby causing a decrease in FoxO acetylation. Our data suggests that FoxO1 has a major PDK4 regulating function. Related to nutrient excess, FoxO1 has a role in regulating fatty acid (FA) uptake and oxidation, and triglyceride storage by mechanisms that are largely unresolved. We examined the mechanism behind palmitate (PA) induced TG accumulation in cardiomyocytes. PA treated cardiomyocytes showed substantial increase in TG accumulation, accompanied by amplification in nuclear migration of phospho-p38 and FoxO1, iNOS induction and translocation of CD36 to the plasma membrane. PA also increased Cdc42 protein and its tyrosine nitration, there by re-arranging the cytoskeleton and facilitating CD36 translocation. Cardiomyocyte cell death is a major contributing factor for diabetic cardiomyopathy, and multiple mechanisms have been proposed for its initiation. Diabetes increased the nuclear content of FoxO1 as a result of attenuated survival signalling. Increased nuclear FoxO1 augmented iNOS induction in the diabetic myocardium. The iNOS induced nitrosative stress increased the nitrosylation of GAPDH accompanied by its binding to Siah1 and translocation to the nucleus with an increased nuclear nitrosative stress. iNOS also nitrosylated caspase-3 there by hindering its ability to cleave PARP, a direct downstream target of Caspase-3. The resultant effect is activation of PARP with an nuclear compartmentalization of Apoptosis Inducing Factor (AIF) and resultant cell death.
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Platt, Thomas. "LEPTIN RESISTANCE INDUCED OBESITY AND DIABETES PROMOTE NEUROPATHOLOGICAL CHANGES IN THE AGING BRAIN." UKnowledge, 2014. http://uknowledge.uky.edu/biochem_etds/18.
Анотація:
The aging brain is prone to the development of pathology and dementia. With a rapidly growing elderly population diagnoses of neurodegenerative diseases, such as Alzheimer’s disease (AD), frontotemporal dementia (FTD), and Parkinson’s disease are on the rise. Additionally, diabetes and obesity are linked to an increased risk of dementia. The convergence of this increasingly aged population with the obesity and diabetes epidemic give rise to new concerns regarding the future of prevention and treatment of neurodegenerative diseases. Our lab has previously shown that leptin, an adipokine involved in signaling satiety to the hypothalamus, can modulate the generation of the amyloid beta (Aβ) peptide (a toxic peptide associated with neurologic disease) and attenuate hyperphosphorylation of the tau protein (another peptide prone to forming large insoluble structures causing neurodegeneration). From these studies we have elucidated that leptin resistant mice (which develop severe obesity and type-2 diabetes mellitus) with knock-in mutations for the amyloid precursor protein (APP) and presenilin-1 (PS1) genes develop extensive vascular pathology and cognitive impairments. Interestingly, these mice do not display increased levels of amyloid deposition in the brain. Additionally, increased tau phosphorylation occurs in these mice with leptin resistance. As a follow up to this study db mice were transduced, via adeno-associated virus, with the tau P301L mutant to induce the development of tangle pathology. These mice displayed no cognitive deficits, yet they displayed increases in both tau phosphorylation and tangle count within the hippocampus. Collectively, these studies indicate leptin resistance, obesity, and type-2 diabetes mellitus promote the development of cerebrovascular and neurofibrillary tangle pathologies associated with neurodegeneration and dementia. These observations open many previously unexplored avenues for developing novel therapeutics to treat these devastating diseases.
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Turner, Daniel. "Impact of acute resistance exercise on glycaemia in individuals with type 1 diabetes." Thesis, Swansea University, 2015. https://cronfa.swan.ac.uk/Record/cronfa43149.
Анотація:
The impact of acute resistance exercise (RE) on glycaemia in type 1 diabetes (T1DM) individuals is poorly understood. Yet, such knowledge would have great use in improving our understanding of blood glucose control during and after the performance of RE. Increasing research in this area might help minimise complications associated with blood glucose vulnerability and potentially maximise health benefits related to RE which are known to be obtained by people without diabetes. The overarching aim of this thesis was to examine the impact of acute RE on glycaemia in T1DM individuals, and promote confidence in people with T1DM to partake in this form of exercise and lead a more physically active lifestyle. Exercise volume, or the total weight lifted during a RE session, is a primary component in the design of a RE session. Therefore, Chapter 3 examined the acute impact of manipulating RE session volume in T1DM individuals. The results demonstrate that exercise volume is an important factor in determining the blood glucose responses to RE; specifically, blood glucose concentrations rose above rest for one hour after one and two sets of similar intensity RE, but this exercise-induced hyperglycaemia was attenuated by increasing the volume of exercise by addition of a similar intensity third set of RE. Additionally, performing morning RE after an overnight fast and in the absence of rapid-acting insulin, did not induce acute hypoglycaemia, ketoacidosis or raise a marker of muscle damage, but caused metabolic acidosis in a dose-dependent fashion. Exercise intensity is a characteristic that is integral to the design of a RE session, and this characteristic might play a role in explaining the exercise-induced hyperglycaemia caused by the thirty minute (two-set) RE sessions in Chapter 3. The aim of Chapter 4 was to examine the impact of manipulating exercise intensity in T1DM individuals. The findings from this study demonstrate that performing a low intensity RE session evoked a similar magnitude of post-exercise hyperglycaemia and metabolic acidosis than a higher intensity RE session, when sessions were matched for total weight lifted. In an attempt to alleviate the consistent exercise-induced hyperglycaemia presented by the two-set RE session, the aim of Chapter 5 was to implement a modified algorithm that delivers an individualized dose of rapid-acting insulin after morning RE, to counter acute post-exercise hyperglycaemia in T1DM individuals. The results demonstrate that post-exercise rapid-acting insulin injection delivered by means of an algorithm resulted in reductions to post-RE hyperglycaemia without the occurrence of hypoglycaemia during two hours after exercise. However, during the subsequent twenty hours of freely living conditions, T1DM individuals remained unprotected from post-exercise hypoglycaemia as per a control condition. Overall, the findings of this thesis underpin some important factors that determine the glycaemic and metabolic responses to acute performance of RE, which may facilitate the better management of blood glucose around this form of exercise, in T1DM individuals.
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Kudiarasu, Christine. "Effects of eccentric versus concentric resistance training in adults with Type 2 Diabetes." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2020. https://ro.ecu.edu.au/theses/2297.
Анотація:
The benefits of resistance training for people with Type 2 diabetes (T2D) are well documented; however, the effects of different muscle contraction types (e.g. eccentric, concentric) on physiological outcomes for this population are still unclear. This study investigated the effects of eccentric (ECC) versus concentric (CON) resistance training on blood markers, muscle strength, physical functional performance and body composition. Eighteen adults with T2D (Age: 64.8 ± 9.0 y; BMI: 30.3 ± 4.1 kg/m2) were randomly assigned to either an ECC (n = 9) or a CON (n = 9) group. Participants performed 2 or 3 sets of 10 eccentric (5-s) or concentric (2-s) contractions of eight upper and lower body resistance exercises, twice a week for 12 weeks. Training intensity gradually increased from 10 to 100% of 1-repetition maximum concentric strength (1-RM) for the ECC group and from 50 to 100% of 1-RM strength for the CON group, based on the 1-RM at baseline. Blood markers (glucose, insulin, HbA1c, HOMA2-IR, cholesterol, triglycerides, HDL and LDL), muscle strength (1- RM), body composition (dual-energy x-ray absorptiometry), and physical functional performance tests consisting of 6-min walk (6MWT), chair rise (CR), timed up-and-go (TUG), and balance were measured before and after the intervention, and the changes were compared between groups. Significant differences in the improvement between the ECC and CON group were found for 1-RM strength for bicep curl (ECC: 11%, CON: 27%), calf raise (ECC: 37%, CON: 68%) and abdominal crunch (ECC: 22%, CON: 42%) exercises, hip circumference (ECC: -1%, CON: -5%) and SF-36 pain measures (ECC: 6%, CON: -1%). Muscle strength significantly increased more for the CON group (27–68%) than the ECC group (12–37%) which was likely due to greater combined total load lifted in the CON (143,262 ± 57,972 kg) than the ECC group (111,678 ± 51,225 kg). Significant improvements (p < 0.05) were also found in the ECC group for the 6MWT (56.8 ± 2.2 m), TUG (-0.8 ± 0.3 s) and CR (-1.8 ± 1.4 s), while the CON group significantly improved the 6MWT (63.4 ± 12.0 m) and CR (-2.3 ± 1.6 s). Total equilibrium balance increased by 7.0% in the ECC group and 4.3% in the CON group. Body composition improved similarly for both groups including significant reductions in total fat mass (ECC: -2.0 ± 1.3 kg, CON: -2.2 ± 1.2 kg) and significant increase in total lean mass (ECC: 1.8 ± 0.7 kg, CON: 2.0 ± 0.2 kg). No significant changes were found in blood markers for both groups. These results showed that ECC training performed at lower intensities (RPE: 4.1 ± 2.1) was as effective as CON training for improving physical functional performance, strength and body composition. These findings suggest that focusing on eccentric contractions in resistance training is beneficial and well-tolerated in adults with T2D.
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Frangioudakis, Georgia St Vincent's Clinical School UNSW. "Insulin signal transduction in vivo in states of lipid-induced insulin resistance." Awarded by:University of New South Wales. St Vincent's Clinical School, 2004. http://handle.unsw.edu.au/1959.4/27419.
Анотація:
Insulin resistance is the major metabolic defect in obesity and Type 2 diabetes. Increased lipid accumulation is strongly associated with insulin resistance. A significant component of insulin resistance is thought to be a reduced ability of insulin to activate the cascade of phosphorylation events that lead to the metabolic effects of this hormone. The broad aims of this thesis were to examine the effect of high-fat diets containing different fat subtypes on in vivo insulin signalling, under conditions normally used to detect whole body insulin resistance, and to compare the effects of acute and chronic lipid oversupply on insulin signalling in vivo. Time-course and dose-response effects of insulin stimulation on site-specific phosphorylation of key signalling proteins were studied in rat tissues in vivo, to establish an appropriate experimental system to examine the onset of activation of the insulin signalling pathway. It was determined that short insulin infusions with concurrent glucose infusion, similar to the beginning of a euglycaemic-hyperinsulinaemic clamp, significantly increased the phosphorylation of major intermediates of the insulin signalling pathway in important tissues of insulin action (skeletal muscle [RQ], liver [LIV] and white adipose tissue [EPI]). These experiments provided a platform to study insulin signalling under the same conditions used to study lipid-induced insulin resistance. The provision of diets enriched in polyunsaturated or saturated fatty acids (FA) resulted in the corresponding enrichment of these fat subtypes in rat plasma and tissues. However, the effects on insulin signalling were essentially the same. Both fat diets induced defects in sitespecific phosphorylation of insulin receptor substrate (IRS)-1 and protein kinase B (PKB) in RQ and LIV, but not EPI. This suggests that the amount of fat in the diet, rather than enrichment in a particular fat subtype, had a greater impact on the development of signalling defects and that the response to high-fat feeding was tissue-specific. A 3hr elevation of circulating FA (using a lipid/heparin infusion), to a level that is relevant in clinical Type 2 diabetes, impaired insulin-stimulated PKB phosphorylation with no significant effect on IRS-1 phosphorylation. This suggests that there may be differences in the way acute and chronic exposure to increased FA impair insulin signalling. The phosphorylation defects observed in both chronic and acute studies did not seem to be associated with activation of major stress signalling pathways (JNK and NFkB), which have been suggested to have a role in lipidinduced insulin resistance. In conclusion, these studies demonstrate that impaired IRS-1 and PKB phosphorylation do have a role in the reduced insulin action observed with lipid oversupply in vivo, because the changes were detected under similar conditions as those used to determine whole body insulin resistance.
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Sharma, Divya. "Drug Delivery Systems for Treatment of Diabetes Mellitus." Diss., North Dakota State University, 2019. https://hdl.handle.net/10365/31745.
Анотація:
Daily injections for basal insulin therapy are far from ideal resulting in hypo/hyperglycemic episodes associated with fatal complications in type-1 diabetes patients. The purpose of this study was to develop a thermosensitive copolymer-based in situ depot forming delivery system to provide controlled release of insulin for extended duration following a single subcutaneous injection, closely mimicking physiological basal insulin requirement. Size and nature of the incorporated therapeutic were observed to affect the release profile of insulin. Modification with zinc and chitosan preserved thermal, conformational, and chemical stability of insulin during the entire duration of storage (up to 9 months at 4 °C) and release (up to 3 months at 37 °C). In vivo, daily administration of long-acting insulin, glargine, resulted in fluctuating blood glucose levels between 91 – 443 mg/dL in type 1 diabetic rats. However, single administration of oleic acid-grafted-chitosan-zinc-insulin complexes incorporated in copolymer formulation demonstrated slow diffusion of insulin complexes maintaining peak-free basal insulin level of 21 mU/L for 91 days. Sustained release of basal insulin also correlated with efficient glycemic control (blood glucose <120 mg/dL), prevention of diabetic ketoacidosis and absence of cataract development, unlike other treatment groups. The suggested controlled basal insulin delivery system has the potential to significantly improve patient compliance by improving glycemic control and eliminating life-threatening diabetes complications.
Furthermore, oleic acid-grafted-chitosan (CO) nanomicelles were investigated as a non-viral vector to deliver plasmid DNA encoding short hairpin RNA (shRNA) against pro-inflammatory cytokines to adipose tissue macrophages and adipocytes for the treatment of insulin resistance. Nanomicelles modified using mannose (COM) and adipose homing peptide (AHP) (COA) showed significantly higher uptake and transfection efficiency in inflamed macrophages- adipocytes co culture owing to glucose transporter-1 and prohibitin receptor mediated internalization, respectively. Ligand modified nanomicelles loaded with shRNA against tumor necrosis factor alpha (COM-TNFα) and monocyte chemoattractant protein-1 (COA-MCP1) demonstrated significant attenuation of pro-inflammatory cytokines and improved insulin sensitivity and glucose tolerance in obese-diabetic mice for six weeks post treatment with single dose of optimized formulation. Overall, chitosan nanomicelles mediated targeted gene therapy can help attenuate inflammation, the chief underlying cause of insulin resistance, thereby helping reverse the progression of diabetes.National Institutes of Health (NIH) grant R15GM114701
ND EPSCoR seed award FAR0030636
41
McConnell, Elizabeth Mae. "Increased vascular disease in adult hypopituitarism : studies of mortality, insulin resistance and endothelial function." Thesis, Queen's University Belfast, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301743.
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Talbot, Nicola A. "Obesity, inflammation and insulin resistance in skeletal muscle." Thesis, Royal Veterinary College (University of London), 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.618327.
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Andersen, Ditte K. "The role of microRNAs in skeletal muscle insulin resistance." Thesis, Royal Veterinary College (University of London), 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.701676.
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Nowak, Christoph. "Insulin Resistance : Causes, biomarkers and consequences." Doctoral thesis, Uppsala universitet, Molekylär epidemiologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-316891.
Анотація:
The worldwide increasing number of persons affected by largely preventable diseases like diabetes demands better prevention and treatment. Insulin is required for effective utilisation of circulating nutrients. Impaired responsiveness to insulin (insulin resistance, IR) is a hallmark of type 2 diabetes and independently raises the risk of heart attack and stroke. The pathophysiology of IR is incompletely understood. High-throughput measurement of large numbers of circulating biomarkers may provide new insights beyond established risk factors. The aims of this thesis were to (i) use proteomics, metabolomics and genomics methods in large community samples to identify biomarkers of IR; (ii) assess biomarkers for risk prediction and insights into aetiology and consequences of IR; and (iii) use Mendelian randomisation analysis to assess causality. In Study I, analysis of 80 circulating proteins in 70-to-77-year-old Swedes identified cathepsin D as a biomarker for IR and highlighted a tentative causal effect of IR on raised plasma tissue plasminogen activator levels. In Study II, nontargeted fasting plasma metabolomics was used to discover 52 metabolites associated with glycaemic traits in non-diabetic 70-year-old men. Replication in independent samples of several thousand persons provided evidence for a causal effect of IR on reduced plasma oleic acid and palmitoleic acid levels. In Study III, nontargeted metabolomics in plasma samples obtained at three time points during an oral glucose challenge in 70-year-old men identified associations between a physiologic measure of IR and concentration changes in medium-chain acylcarnitines, monounsaturated fatty acids, bile acids and lysophosphatidylethanolamines. Study IV provided evidence in two large longitudinal cohorts for causal effects of type 2 diabetes and impaired insulin secretion on raised coronary artery disease risk. In conclusion, the Studies in this thesis provide new insights into the pathophysiology and adverse health consequences of IR and illustrate the value of combining traditional epidemiologic designs with recent molecular techniques and bioinformatics methods. The results provide limited evidence for the role of circulating proteins and small molecules in IR and require replication in separate studies and validation in experimental designs.
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Alkhalidy, Hana Awwad. "Flavonol kaempferol in the regulation of glucose homeostasis in diabetes." Diss., Virginia Tech, 2016. http://hdl.handle.net/10919/82485.
Анотація:
Diabetes mellitus is a major public health concern. Although the accessible novel drugs, techniques, and surgical intervention has improved the survival rate of individuals with diabetes, the prevalence of diabetes is still rising. Type 2 diabetes (T2D) is a result of chronic insulin resistance (IR) and loss of β-cell mass and function. Therefore, the search for naturally occurring, low-cost, and safe compounds that could enhance insulin sensitivity and protect functional β-cell mass can be an effective strategy to prevent this disease. Kaempferol, a flavonol present in various medicinal herbs and edible plants, has been shown to elicit various pharmacological activities in preclinical studies. However, studies investigating the effect of kaempferol on diabetes are limited. In this dissertation, I explored the anti-diabetic potential of dietary intake of kaempferol in diet-induced obese mice and insulin-deficient diabetic mice.
First, kaempferol was supplemented in the diet to determine whether it can prevent IR and hyperglycemia in high fat (HF) diet-induced obese mice or STZ-induced obese diabetic mice. To evaluate its efficacy for treating diabetes, kaempferol was administrated once daily via oral gavage to diet-induced obese and insulin-resistant mice or lean STZ-induced diabetic mice. The results demonstrated that long-term oral administration of kaempferol prevents HFD-induced metabolic disorders in middle-aged obese mice. Oral administration of kaempferol improved glucose intolerance and insulin sensitivity, and this effect was associated with increased Glut4 and AMPKa expression in muscle and adipose tissues. Consistent with our findings from the in iii vitro study in C2C12 muscle cell line, these findings suggest that kaempferol may reduce IR at the molecular level by improving glucose metabolism in peripheral tissues. In the second study, dietary kaempferol supplementation prevented hyperglycemia and glucose intolerance by protecting β-cell against the induced damage in obese STZ-induced diabetic mice. In the third study, the administration of kaempferol by oral gavage significantly ameliorated hyperglycemia and glucose intolerance and reduced the incidence of diabetes from 100 % to 77.8% in lean STZinduced diabetic mice. This kaempferol effect was associated with reduced hepatic glucose production, the primary contributor to hyperglycemia, and increased glucose oxidation in the muscle of diabetic mice. Kaempferol treatment restored hexokinase activity in the liver and skeletal muscle and reduced pyruvate carboxylase (PC) activity and glycogenolysis in the liver.
Unlike its effect on T2D mice, kaempferol effect in lean STZ-induced diabetic mice was not associated with changes in plasma insulin levels. In the last study, we found that administration of kaempferol by oral gavage significantly improved blood glucose control by suppressing hepatic glucose production and improving glucose intolerance in obese insulin-resistant mice. Similar to its effect in old obese mice, kaempferol enhanced whole-body insulin sensitivity. Kaempferol increased Akt and hexokinase activity and decreased PC activity in the liver. However, kaempferol did not exert any changes in glucose metabolism or insulin sensitivity when administered to healthy lean mice. Overall, findings from these studies provide new insight into the role of kaempferol in the regulation of glucose homeostasis and suggest that kaempferol may be a naturally occurring anti-diabetic compound by improving insulin sensitivity, improving glucose regulation and metabolism, and preserving functional β-cell mass.Ph. D.
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Negrato, Carlos Antonio [UNESP]. "Hiperglicemia gestacional leve como fator de risco para síndrome metabólica na gravidez e morbilidade perinatal." Universidade Estadual Paulista (UNESP), 2006. http://hdl.handle.net/11449/104174.
Анотація:
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Em 1988, Reaven descreveu a síndrome X, uma junção de diversos fatores de risco para as doenças cardiovasculares, sendo a resistência à insulina o ponto de partida para o estabelecimento de tais fatores. Várias denominações foram dadas a este grupo de comorbidades e hoje ela é conhecida como Síndrome Metabólica. Seu estudo tem sido dificultado pela ausência de consenso na sua definição. Sua prevalência varia de acordo com o critério diagnóstico utilizado e com as características da população estudada, sendo mais encontrada em portadores de obesidade central. A prevalência em mulheres varia de 10,7% a 40,5%, e é um preditor para o desenvolvimento de complicações cardiovasculares, estando associada a duas importantes entidades nosológicas bastante estudadas em ginecologia e obstetrícia: a síndrome dos ovários policísticos e o diabetes gestacional. Embora não façam parte dos critérios diagnósticos, várias condições clínicas e fisiopatológicas estão freqüentemente a ela associadas, tais como: acantose nigricans, doença hepática gordurosa não-alcoólica, microalbuminúria, estados pró trombóticos (elevação dos níveis de PAI-1 e fibrinogênio), estados pró- inflamatórios (elevação dos níveis de IL-6, TNF-a, resistina e PC-R), disfunção endotelial e hiperuncemia. Os autores fazem uma revisão sobre o diagnóstico laboratorial e os fatores ligados a SM evidenciando que a Critósos diagnósticos atuais da síndrome metabólica gravidez é um modelo da SM compensada e sugerem que o diabetes gestacional e a hipergilcemia materna diária devam ser acrescentados aos critérios diagnósticos.
In 1988, Reaven described the Syndrome X, a junction of several risk factors for cardiovascular diseases, being the insulin resistance the set point for the establishment of such factors. Many denominations were given to this group of co-morbidities and today it is known as metabolic syndrome. lts study has been difficult by the absence of a consensus for its definition. lts prevalence vanes according to the diagnostic criterion used and with the characteristics of the studíed population, being found mainly in people with central obesity. The prevalence in women varies from 10.7% to 40.5%, and it is a predictor of cardiovascular complications associated with two important nosologic entities concerned with gynecology and obstetrics: the polycystic ovaries syndrome and gestational diabetes. A variety of clinical and physiopathoiogical conditions are frequently associated to it. These are: acanthosis nigricans, non alcoholic fatty tiver disease, microalbuminuria, prothrombotic states (elevation of PAI-1 and fibrinogen leveIs), proinflammatory states (elevation of IL-6, TNF-a, resistin and C-RP leveis), endothelial dysfunction and hyperuricemia. The authors make a revision on the laboratorial diagnosis and the factors Iinked to the metabolic syndrome and attest that pregnancy is a counterbalanced model of the syndrome Critérios diagnósticos atuaiS da 5ifldrOme metabólica and suggest that gestational diabetes and diurnal maternal hyperglycemia should be added to the diagnostic criteria.
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Dumais, Valerie. "Insulin Resistance, Metabolic Syndrome and Diabetes in Women at High Risk for Breast Cancer." Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31508.
Анотація:
Purpose: The overall objective of this prospective study was to quantify the prevalence of insulin resistance (IR), metabolic syndrome (MetS) and type 2 diabetes (T2D) in women at high risk for breast cancer, stratified by menopausal status. We also aimed to calculate the sample size required for a future case-control study comparing these prevalences to those of the general population. Methods: Participants consisted of 100 Caucasian women above the age of 35 with an estimated 5yr risk of breast cancer ≥1.7%. A comprehensive metabolic profile was obtained for each participant based on a questionnaire, fasting blood sample and biophysical measurements. Results: In comparison to published prevalence’s of IR, MetS and T2D in the general population, the prevalence of IR and MetS is higher in our study sample. High risk postmenopausal women have a higher prevalence of body mass index, waist circumference, MetS and hypertension than premenopausal women. We have shown a significant correlation between Gail score and high-density lipoprotein cholesterol. Conclusions: The sample size calculation, based on the prevalence’s obtained in the present study, support the significance and feasibility of a future case control study comparing the prevalence of IR and MetS in women at high risk and average risk for breast cancer. Further studies are needed to clarify the underlying mechanisms for the association between IR, MetS, T2D and breast cancer risk.
48
Mårdberg, Emelie. "Effect of Resistance Training in Patients with Type 2 Diabetes Mellitus : − A Systematic Review." Thesis, Örebro universitet, Institutionen för läkarutbildning, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-37001.
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Agbaje, Olorunsola Fatai. "Modelling methodologies to assess insulin resistance and insulin secretion in type 2 diabetes subjects." Thesis, City University London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.397933.
50
Direk, Kenan. "The role of mitochondria in the development of insulin resistance and type 2 diabetes." Thesis, King's College London (University of London), 2013. https://kclpure.kcl.ac.uk/portal/en/theses/the-role-of-mitochondria-in-the-development-of-insulin-resistance-and-type-2-diabetes(30f426ed-9221-473f-b177-acefda85acaa).html.
Анотація:
This thesis explores three broad areas of interest in the pathophysiology of type 2 diabetes (T2D). The first part of the thesis examines the relative contributions of body fat measurements on T2D and related morbidities in a large cohort of twins. A proxy measure of visceral fat was constructed from anthropometric and dual-energy X-ray absorptiometry, its heritability was estimated at 58% using the classical twin model and its influence on morbidity was compared to total abdominal fat and the body mass index. The findings from this work show that intra-abdominal adiposity confers the greatest independent risk on morbidity and appears to almost entirely mediate the observed association between morbidity and all the other measures of adiposity investigated. The second part of this thesis is a candidate gene study of the PARL/ABCC5 gene region motivated by prior evidence suggesting a role for PARL in T2D susceptibility. Using a single marker test of association, SNPs in and around the PARL gene showed no evidence of association with T2D. However, analysis based upon SNPs in the entire gene region (184,743-185,548Kb, build 36) using a multi-marker test of association, provided strong evidence that the neighbouring gene (ABCC5) is associated with T2D in both European and African American samples. In addition, ABCC5 expression in subcutaneous adipose tissue was strongly associated with fasting insulin and glucose serum levels, visceral fat accumulation, and T2D with evidence that the disease susceptibility variant(s) is a regulatory element (an expression quantitative trait locus) located at intron 26 in ABCC5. The third component of this thesis is a comprehensive investigation into the potential role of nuclear-encoded mitochondrial (NEM) genes in the aetiology of T2D. A pathway analysis approach is used to test for enrichment of T2D association signals across the genome in defined NEM gene sets. From this analysis, the biological pathways of glycolysis, the tricarboxylic acid cycle, and mitochondrial translation all show evidence of pathway enrichment. These findings demonstrate for the first time, potential associations between these pathways and T2D susceptibility in European and African American samples.