Добірка наукової літератури з теми "Beta cell preservation"

Clinical islet transplantation requires graft preservation conditions with a minimal loss in viable beta cells. The present study examines whether rat pancreatic beta cells survive a 96 h storage period at 4°C. In a single cell viability assay, less than 20% viable cells were counted after 48 h storage in physiological HAM's F10 medium; cell survival was better in the high potassium solutions UW or Collins and further improved by supplementing Collins with albumin and benzamidine (CAB - 77% viability after 96 h). Suspended beta cell aggregates were also well preserved during 4 days in CAB-4°C as judged from DNA recovery and electron microscopy. After cold-storage in CAB, beta cells exhibited a higher insulin content than after culture in HAM's F10 at 20° or 37°C, but their capacity for subsequent insulin synthesis and release was comparable. When isolated islets were stored in CAB-4°C for 96 h, they yielded slightly higher numbers of dissociated cells than after culture in HAM's F10 at 20°C. Implantation of cold stored islets from 2 donor pancreata corrected hyperglycemia in streptozotocin-diabetic rats. It is concluded that rat beta cells can be stored in a supplemented Collins solution for at least 4 days at 4°C, with preservation of initial cell number, hormone content and glucose responsiveness. During short-term periods, this new storage condition is at least equivalent to cultures at 20° or 37°C. Further studies are needed to assess any advantage for long-term storage of islet cell grafts.

Type 2 diabetes (T2D) is widely considered a chronic and progressive disease without cure. As beta-cell function progressively declines over time, blood glucose rises. Current management of T2D involves incremental introduction of dietary and drug therapies to achieve normoglycaemia. However, recent studies have demonstrated remission of T2D following bariatric surgery, very low calorie diet or intensive insulin therapy, raising the possibility that the declining beta-cell function in T2D may be arrested or even reversed. The point at which such interventions are introduced in the course of T2D is key for clinical benefit. Future treatment strategies should be revised to target early beta-cell preservation and thus disease remission. This article reviews the pathogenesis of beta-cell dysfunction and evidence for the clinical benefit of preserving beta-cell function in T2D, and discusses the evidence for beta-cell preservation of current glucose-lowering therapies with particular reference to their effect when initiated at the time of diagnosis of T2D.

Type 1 diabetes mellitus is the result of the autoimmune response against pancreatic beta-cell(s). At the time of clinical diagnosis near 70% of beta-cell mass is been destroyed as a consequence of the auto-destruction that begins months or even years before the clinical diagnosis. Although marked reduction of chronic complications was seen after development and progression of insulin therapy over the years for type 1 diabetic population, associated risks of chronic end-organ damage and hypoglycemia still remain. Besides tight glucose control, beta-cell mass preservation and/or increase are known to be other important targets in management of type 1 diabetes as long as it reduces chronic microvascular complications in the eyes, kidneys and nerves. Moreover, the larger the beta-cell mass, the lower the incidence of hypoglycemic events. In this article, we discuss some insights about beta-cell regeneration, the importance of regulation of the autoimmune process and what is being employed in human type 1 diabetes in regard to stem cell repertoire to promote regeneration and/or preservation of beta-cell mass.

Indiana University-Purdue University Indianapolis (IUPUI)
Pancreatic insulin-secreting beta cell failure is central to the development of diabetes. Therapeutic applications targeted at understanding and manipulating beta cell destruction mechanisms should enhance the preservation of functional beta cell mass and prevent diabetes. To this end, we have demonstrated that diabetogenic assaults (e.g., endoplasmic reticulum stress, glucolipotoxicity, and pro-inflammatory cytokines) attenuate the activation of beta cell pro-survival signaling pathways via a stress-inducible molecule called Mitogen-inducible gene 6 (Mig6). We discovered that the overabundance of Mig6 exacerbates stress-induced beta cell apoptosis and inhibits insulin secretion. Conversely, the deficiency of Mig6 partially protected beta cells from DNA damage-induced cell death. Further, we established that Mig6 haploinsufficient mice retained islet integrity and function and exhibited greater beta cell mass recovery following treatment with multiple low doses of the beta cell toxin streptozotocin. These data suggest that Mig6 may be a therapeutic target for beta cell preservation in diabetes.

Continued loss of beta cell function is responsible for progressive deterioration of plasma glucose control and complications characteristic of type 2 diabetes. Two classes of incretin-based antihyperglycaemic agents, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1(GLP-1) analogues, have shown favourable effects on beta cell function. The aim of this systematic review was to provide a comprehensive synthesis of randomised clinical studies comparing the effectiveness of GLP-1 analogues to DPP-4 inhibitors in improving beta cell function and managing diabetes related complications. A search of PubMed, EMBASE and national and international clinical trials databases was conducted for randomised controlled trials that compared GLP-1 analogues to DPP-4 inhibitors, either alone or in combination with metformin, in adults with type 2 diabetes. Methodological quality of included studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist, and research data was extracted using the JBI data extraction tool. Outcomes included beta cell function (measured by homeostasis model assessment-beta [HOMA-beta], plasma connecting peptide [C-peptide] and proinsulin to insulin [PI/I] plasma concentration ratio) glycated haemoglobin (HbA1c), fasting and postprandial plasma glucose levels, diabetes related complications, and adverse drug events. Seven randomised controlled trials including 2661 participants were included in this review. The overall quality of included studies was good. Treatment duration ranged from 24 to 52 weeks in the included studies and included a number of different dosages. Results of meta-analysis showed that GLP-1 analogues, at different dosages and duration, were associated with statistically significant improvements in beta cell function compared to DPP-4 inhibitors as measured by HOMA-beta; mean difference 23% and 25% for high dose GLP-1 analogues after 26 and 52 weeks, respectively (p<0.00001); 18.5% and 16.7% for low dose GLP-1 analogues after 26 and 52 weeks, respectively (p<0.00001). Treatment with GLP-1 analogues showed a greater reduction in glycated haemoglobin (HbA1c) compared to treatment with DPP-4 inhibitors: a mean difference of -0.52% and -0.68% (-5.67mmol/moL and - 7.41mmol/moL) for high dose GLP-1 analogues after 26 and 52 weeks, respectively (p<0.00001); and -0.38% and -0.45% (-4.14mmol/moL and -4.91mmol/moL) for low dose GLP- 1 analogues after 26 and 52 weeks, respectively (p<0.00001). Treatment with GLP-1 analogues resulted in a greater reduction in fasting plasma glucose compared to DPP-4 inhibitors: a mean difference of -1.23 mmol/L and -1.47 mmol/L (-22.16 mg/dL and -26.49 mg/dL) for high dose GLP-1 analogues after 26 and 52 weeks, respectively p<0.00001); and -1.01mmol/L and -0.84mmol/L (-18.20mg/dL and -15.13 mg/dL) for low dose GLP-1 analogues after 26 and 52 weeks, respectively (p<0.00001). No studies reported outcomes for diabetes related complications. However, DPP-4 inhibitors were associated with fewer gastrointestinal adverse events compared to GLP-1 analogues. There were no differences in other adverse events such as headache and infection. The findings showed that GLP-1 analogues had greater beneficial effects on pancreatic beta cell function and plasma glucose control than DPP-4 inhibitors, but caused more gastrointestinal adverse events. Longer term safety data is required to better identify the contribution of GLP-1 analogues in reducing diabetes related microvascular complications, and determine their long term pancreatic and cardiac effects.
Thesis (M.Clin.Sc.) -- University of Adelaide, Joanna Briggs Institute, 2016.

A period of several years from the appearance of multiple antibodies to beta-cell antigens to clinical presentation of type 1 diabetes represents a window of opportunity for immunological intervention in order to halt the autoimmune process and preserve beta-cell function. The most rapid loss of beta-cell function happens in the first 12 months after diagnosis, which provides a further opportunity for interventions leading to effective beta-cell preservation. This is important as even a small amount of residual beta-cell function markedly improves metabolic control. Low-risk immunotherapeutic options are now available and widely used in other autoimmune diseases, but no such therapies are licensed for use in type 1 diabetes. With multiple immuno-intervention approaches showing potential efficacy in type 1 diabetes, we are now on the brink of fundamentally changing the management of this burdensome disease by using immunotherapy to preserve endogenous beta-cell function and make metabolic control substantially easier. It seems likely that non-antigen-specific therapies will be licensed first, but antigen-specific therapy may follow, offering the possibility of treating type 1 diabetes in the preclinical phase and delaying or preventing the need for insulin therapy.

Introduction: Immature teratoma represents 3% of all teratomas, 1 % of all ovarian cancers and 20% of malignant ovarian germ cell tumors. It is found either in pure form or as a component of a mixed germ cell tumor. It occurs essentially during the first two decades of life. According to WHO, immature teratoma is defined as a teratoma containing a variable amount of immature embryonal type neuroectodermal tissue Case: We present here a report of 23 years old unmarried female who presented with complaint of abdominal pain since 1 month and her CT scan done outside, showed fibroid uterus. She had history of typhoid fever 1 month back for which USG was done which suggested large uterine fibroid. On examination she was hemodynamically stable. On abdominal examination a non-tender supra-pubic mass of 24 weeks size with firm consistency, irregular margin was felt. On investigation CA 125 was 64.90 IU/L, LD- 223, beta HCG- 1.14. On MRI a large abdomino-pelvic lesion, likely left adnexal lesion with multiple cystic areas, with hemorrhage, with ascites and enlarged retroperitoneal lymph nodes with omental infiltration suggestive of a possibility of malignant germ cell tumor. In view of large ovarian tumor, possibly malignant decision for staging laparotomy was taken. Intra-operatively a large irregular vascular solid mass of 20 x 20 cms with bosselated appearance with few cystic lesions over it was seen, arising from left ovary and was sent for frozen section which reported malignant mature teratoma with components of immature teratoma. She underwent laparotomy with left salpingo-oophorectomy with right ovarian biopsy, omentectomy, appendectomy with B/L pelvic lymphadenectomy. Histopathology was suggestive of grade III immature teratoma. In view of grade III immature teratoma, she received chemotherapy (BEP regimen) post-operatively and is currently under follow up. Conclusion: This case reflects the importance of early diagnosis in cases of pelvic masses in young females. Fertility preservation should be considered in young women with germ cell tumors. Patients with grade II or III tumors or a mere advanced stage disease should be treated with adjuvant chemotherapy (BEP) in addition to surgery.