Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down?

Nauck, Michael A.; Vardarli, İrfan; Deacon, Carolyn F.; Holst, Jens J.; Meier, Juris J.

doi:10.1007/s00125-010-1896-4

Cited by 414 publications

(351 citation statements)

References 72 publications

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“…This suggests functional variations in the two conditions, resembling what happens with glucagon, the release of which is altered in type 2 diabetic islets, despite similar amounts of glucagon-containing cells [38][39][40]. Although type 2 diabetic patients may release less GLP-1, which could contribute to decreased incretin effects in this patient group [1,[41][42][43], it cannot be ruled out that the reduced concentrations of active GLP-1 in such patients might be partly due to increased DPP-4 activity. Increased plasma DPP-4 activity in type 2 diabetic patients has been reported [44], and chronic hyperglycaemia induced higher DPP-4 activity, with reductions of circulating active GLP-1 [45].…”

Section: Discussionmentioning

confidence: 93%

A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets

et al. 2012

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Aims/hypothesis Glucagon-like peptide 1 (GLP-1) is a major incretin, mainly produced by the intestinal L cells, with beneficial actions on pancreatic beta cells. However, while in vivo only very small amounts of GLP-1 reach the pancreas in bioactive form, some observations indicate that GLP-1 may also be produced in the islets. We performed comprehensive morphological, functional and molecular studies to evaluate the presence and various features of a local GLP-1 system in human pancreatic islet cells, including those from type 2 diabetic patients. MethodsThe presence of insulin, glucagon, GLP-1, proconvertase (PC) 1/3 and PC2 was determined in human pancreas by immunohistochemistry with confocal microscopy. Islets were isolated from non-diabetic and type 2 diabetic donors. GLP-1 protein abundance was evaluated by immunoblotting and matrix-assisted laser desorption-ionisation-time of flight (MALDI-TOF) mass spectrometry. Single alpha and beta cell suspensions were obtained by enzymatic dissociation and FACS sorting. Glucagon and GLP-1 release were measured in response to nutrients. Diabetologia (2012) 55:3262-3272 DOI 10.1007/s00125-012-2716 Electronic supplementary material The online version of this article (doi:10.1007/s00125-012-2716-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users. Results Confocal microscopy showed the presence of GLP-1-like and PC1/3 immunoreactivity in subsets of alpha cells, whereas GLP-1 was not observed in beta cells. The presence of GLP-1 in isolated islets was confirmed by immunoblotting, followed by mass spectrometry. Isolated islets and alpha (but not beta) cell fractions released GLP-1, which was regulated by glucose and arginine. PC1/3 (also known as PCSK1) gene expression was shown in alpha cells. GLP-1 release was significantly higher from type 2 diabetic than from nondiabetic isolated islets. Conclusions/interpretation We have shown the presence of a functionally competent GLP-1 system in human pancreatic islets, which resides in alpha cells and might be modulated by type 2 diabetes.

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Section: Discussionmentioning

confidence: 93%

A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets

et al. 2012

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“…Incretin circulating concentrations are often not different between lean, obese and individuals with type 2 diabetes. 19 However, the incretin effect on insulin secretion is blunted in patients with diabetes. 17,20 The administration of exogenous pharmacological doses of GLP-1, or of GLP-1 analogs, restores insulin secretion and lowers blood glucose in patients with diabetes.…”

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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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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“…9 In patients with T2DM, this effect is impaired with the reduction of GLP-1 concentration, although biological potency is maintained. 8,10 Moreover, GLP-1 is rapidly inactivated by the dipeptidyl peptidase-4 (DPP-4) enzyme, which is found abundantly in the vascular endothelium of intestinal lining. Hence GLP-1 action is short lived with a half-life of one to three minutes.…”

Section: Role Of Incretin-based Therapiesmentioning

confidence: 99%