Islet transplantation is an emerging therapeutic option for the\u00a0treatment of select labile type 1 diabetes mellitus patients. The\u00a0announcement of the first consecutive series of successful islet\u00a0transplants in type 1 diabetic patients using the Edmonton Protocol\u00a0sparked renewed interest in the field.<\/p>\n

However, several barriers prevent broad application of islet\u00a0transplantation even within this select patient group. The relatively limited\u00a0availability of cadaveric\u00a0pancreata is especially critical, since not every\u00a0islet isolation attempt currently yields an adequate mass of tissue for\u00a0transplant. Additionally, more than one islet infusion is often necessary to\u00a0achieve insulin independence. Genetically modified tissue and alternative\u00a0sources of insulin secreting tissue (porcine or otherwise) could be longterm solutions to this problem. However, many centers are seeking\u00a0augmentative therapy to islet transplantation. The ideal candidate would\u00a0both reduce the amount of islet tissue needed to render and maintain the\u00a0patient insulin independent and be appropriate for concurrent use with\u00a0immunosuppressive therapy.<\/p>\n

Recent reports, including from a multi-center trial of the Edmonton\u00a0Protocol, show that graft function declines markedly in transplanted\u00a0patients with time. This evanescence of islet graft function may be\u00a0the combined result of allograft rejection, autoimmune diabetes recurrence\u00a0or islet metabolic burnout.\u00a0Immunosuppressive agents, although beneficial in preventing islet\u00a0rejection, may have side effects including diminishing islet function or\u00a0inducing islet death. Although initial reports suggested that sirolimus, one\u00a0such immunosuppressive drug, did not have detrimental effect on islet\u00a0function, several recent investigations have shown that sirolimus has\u00a0a negative impact on (3-cell function by directly reducing viability,\u00a0preventing VEGF-mediated angiogenesis, and preventing neogenesis of\u00a0B-cells from co-transplanted ductal cells.<\/p>\n

Glucagon-like peptide 1 (GLP-1) receptor agonists are emerging\u00a0therapeutic options in the field of type 2 diabetes. GLP-1, an incretin\u00a0hormone, exerts effects through the specific GLP-1 receptor (GLP-1 R),\u00a0including stimulation of insulin secretion, suppression of glucagon\u00a0secretion, slower gastric emptying, and increased satiety. Native GLP-1\u00a0administration has limited therapeutic benefit due to its short biological
\nhalf-life (several minutes). However, GLP-1 analogues, including\u00a0exenatide<\/a> (half-life 60-90 minutes) and liraglutide<\/a> (half-life 13 hours when\u00a0administered subcutaneous) are more promising candidates. GLP-1\u00a0analogues have recently been discovered to have beneficial effects as\u00a0adjunct therapy in type 1 diabetes mellitus models, and in\u00a0pancreatic islet transplant pre-clinical models. Furthermore, some\u00a0groups have studied these analogues in human islet transplantation which\u00a0has provided evidence that isolated islets remain responsive to GLP-1\u00a0receptor agonists. Liraglutide is an especially attractive candidate\u00a0for islet transplantation, in addition to its long half-life, it has been reported\u00a0to maintaining glycemic control in type 2 diabetes with a low risk of\u00a0hypoglycemia.<\/p>\n

However, current literature on the therapeutic role for GLP-1\u00a0analogues is limited to observational rather than mechanistic studies in\u00a0islet transplantation. Furthermore, there is need to understand whether\u00a0documented functional effects of GLP-1 analogues in islet transplant can\u00a0circumvent immunosuppressive toxicities on islets, especially those of\u00a0sirolimus which are of particular concern and have been well described\u00a0elsewhere.<\/p>\n

The article\u00a0report the\u00a0investigation of liraglutide in islet transplantation. It investigated both the effect of liraglutide on islet engraftment in the short\u00a0and long term. Furthermore, it\u00a0investigated the mechanism of liraglutide\u00a0action in the setting of islet transplantation. Finally, it\u00a0sought to investigate\u00a0the ability of liraglutide to improve islet engraftment in the presence of the\u00a0immunosuppressive agent sirolimus at clinically relevant blood levels.<\/p>\n

 <\/p>\n

Reference:<\/p>\n

SHAHEED MERANI.\u00a0ENGRAFTMENT AND FUNCTION\u00a0IN PANCREATIC ISLET TRANSPLANTATION<\/p>\n","protected":false},"excerpt":{"rendered":"

Islet transplantation is an emerging therapeutic option for the\u00a0treatment of select labile type 1 diabetes mellitus patients. The\u00a0announcement of the first consecutive series of successful islet\u00a0transplants in type 1 diabetic …<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[75],"tags":[78,76,77],"_links":{"self":[{"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/posts\/427"}],"collection":[{"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/comments?post=427"}],"version-history":[{"count":2,"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/posts\/427\/revisions"}],"predecessor-version":[{"id":432,"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/posts\/427\/revisions\/432"}],"wp:attachment":[{"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/media?parent=427"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/categories?post=427"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.creative-peptides.com\/blog\/wp-json\/wp\/v2\/tags?post=427"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}