Role of Endogenous Glucagon-Like Peptide-1 in Islet Regeneration After Partial Pancreatectomy

León, Diva D. De; Deng, Shaoping; Madani, Reza; Ahima, Rexford S.; Drucker, Daniel J.; Stoffers, Doris A.

doi:10.2337/diabetes.52.2.365

Cited by 169 publications

(120 citation statements)

References 46 publications

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“…[22][23][24][25] A recent study in pigs showed increased islet number and β-cell proliferation after RYGBP, in parallel with a rise in GLP-1, demonstrating the effect of RYGBP on the plasticity of the endocrine pancreas in this animal model. 43 Whether this is true in humans is unknown.…”

Section: Rygbp Alters Incretin Physiology Rygbp Enhances Incretin Relmentioning

confidence: 73%

“…21 Both GLP-1 and GIP have a trophic effect on the β-cell, as demonstrated in vitro and in vivo in rodent studies. [22][23][24][25] GLP-1 has other important physiological effects, including potentiation of GSIS in the post-prandial setting, suppression of glucagon, slowing of gastric emptying, decrease of body weight and favorable cardiovascular protection, 1,26 that makes it an attractive tool for the treatment of overweight or obese individuals with diabetes. The half-life of GLP-1 and GIP is only few minutes and both incretins are rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4).…”

Section: Importance Of the Incretin Effect In Physiologymentioning

confidence: 99%

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Bariatric surgery and obesity: influence on the incretins

Laferrère

2016

Int J Obes Supp

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The gut hormone incretins have an important physiological role in meal-related insulin release and post-prandial glucose control. In addition to weight loss, the incretin hormones have a role in glucose control after bariatric surgery. The release of incretins, and specifically of glucagon-like peptide (GLP)-1, in response to the ingestion of nutrients, is greatly enhanced after gastric bypass (RYGBP). The rapid transit of food from the gastric pouch to the distal ileum is responsible for the greater GLP-1 release after RYGBP. The incretin effect on insulin secretion, or the greater insulin response to oral glucose compared to an isoglycemic intravenous glucose challenge, is severely impaired in patients with type 2 diabetes, but is recovered rapidly after RYGBP. The improvement in insulin secretion rate and β-cell sensitivity to oral glucose after RYGBP is mediated by endogenous GLP-1, and is abolished by exendin 9-39, a specific GLP-1 receptor antagonist. While calorie restriction and weight loss have major effects on the rapid and sustained improvement of fasted glucose metabolism, the enhanced incretin effect is a key player in post-prandial glucose control after RYGBP.

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Section: Rygbp Alters Incretin Physiology Rygbp Enhances Incretin Relmentioning

confidence: 73%

Section: Importance Of the Incretin Effect In Physiologymentioning

confidence: 99%

Bariatric surgery and obesity: influence on the incretins

Laferrère

2016

Int J Obes Supp

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“…For example, GLP-1 increased beta-cell mass when injected into C57Bl/6 and db/db mice [18,20], but overexpression of exendin-4 in C57BL/6×SJL mice had no effect on islet size [50]. Moreover, antagonist-mediated prevention of GLP-1 action does not affect islet mass in Balb/c mice, although islet growth and topography are abnormal in GLP-1 receptor null CD1 mice [51,52].…”

Section: Discussionmentioning

confidence: 99%

Glucagon-like peptide-1 regulates proliferation and apoptosis via activation of protein kinase B in pancreatic INS-1 beta cells

et al. 2004

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Aims/hypothesis. The incretin hormone glucagon-like peptide-1 augments islet cell mass in vivo by increasing proliferation and decreasing apoptosis of the beta cells. However, the signalling pathways that mediate these effects are mostly unknown. Using a clonal rat pancreatic beta cell line (INS-1), we examined the role of protein kinase B in mediating beta-cell growth and survival stimulated by glucagon-like peptide-1. Methods. Immunoblot analysis was used to detect active (phospho-) and total protein kinase B. Proliferation was assessed using 3 H-thymidine incorporation, while apoptosis was quantitated using 4′-6-diamidino-2-phenylindole staining and APO percentage apoptosis assay. Kinase-dead and wild-type protein kinase B was introduced into cells using adenoviral vectors. Results. Glucagon-like peptide-1 rapidly activated protein kinase B in INS-1 cells (by 2.7±0.7-fold, p<0.05). This effect was completely abrogated by inhibition, with wortmannin, of the upstream activator of protein kinase B, phosphatidylinositol-3-kinase. Glucagon-like peptide-1 also stimulated INS-1 cell proliferation in a dose-dependent manner (by 1.8±0.5-fold at 10 −7 mol/l, p<0.01), and inhibited staurosporine-induced apoptosis (by 69±12%, p<0.05). Both of these effects were also prevented by wortmannin treatment. Ablation of protein kinase B by adenovirus-mediated overexpression of the kinase-dead form of protein kinase Bα prevented protein kinase B phosphorylation and completely abrogated both cellular proliferation (p<0.05) and protection from drug-induced cellular death (p<0.01) induced by glucagon-like peptide-1. Conclusions/interpretation. These results identify protein kinase B as an essential mediator linking the glucagon-like peptide-1 signal to the intracellular machinery that modulates beta-cell growth and survival. [Diabetologia (2004) 47:478-487]

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“…Regeneration was impaired in the GLP-1R −/− mice (De Leon et al, 2003) ZDF fa/fa rats 60% Partially pancreatectomized…”

Section: % Partial Pancreatectomy Balb/c Mice and Glp-1r −/−mentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

557

446

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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Role of Endogenous Glucagon-Like Peptide-1 in Islet Regeneration After Partial Pancreatectomy

Cited by 169 publications

References 46 publications

Bariatric surgery and obesity: influence on the incretins

Bariatric surgery and obesity: influence on the incretins

Glucagon-like peptide-1 regulates proliferation and apoptosis via activation of protein kinase B in pancreatic INS-1 beta cells

Mechanisms of action of glucagon-like peptide 1 in the pancreas

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