Abstract
Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion from pancreatic beta cells and suppresses glucagon secretion from alpha cells. It remains controversial, however, whether GLP-1 receptor (GLP-1R) is expressed in mature alpha cells. In this study, unlike previous studies using non-diabetic animals, we demonstrated using diabetic model rats and confocal laser scanning microscopy that the GLP-1/GLP-1R complex was located in the endosome of diabetic islets. In addition, we showed that GLP-1 and GLP-1R co-localized with various endosomal markers and adenylate cyclase in the alpha cells of diabetic rats. Diabetic rats had endosomal signaling pathway but normal rats had classical signaling pathway for activated GLP-1R. Furthermore, we performed pancreatic perfusion to assess the functional activity of GLP-1R when stimulated by exendin-4 (EX4). In a pancreas perfusion study, EX4 significantly stimulated glucagon secretion in diabetic rats but not normal rats. However, such glucagon secretion was immediately suppressed, probably due to concomitantly secreted insulin. The GLP-1/GLP-1R complex appears to function through an intra-islet paracrine mechanism in diabetic conditions which could explain, at least in part, the mechanism of paradoxical hyperglucagonaemia in type 2 diabetes.
Highlights
Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion from pancreatic beta cells and suppresses glucagon secretion from alpha cells
The aim of this study was to examine whether GLP-1 receptor (GLP-1R) is present in alpha cells under diabetic conditions
Since we used no detergent or antigen retrieval reagent in this endosomal co-localization study to avoid destroying the structure of endosomes, in this system, it is very difficult to detect the expression of GLP-1R, which should be present on beta cell membranes
Summary
Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion from pancreatic beta cells and suppresses glucagon secretion from alpha cells. It has been reported that GLP-1 and GLP-1R agonist secrete insulin from beta cells, which suppresses glucagon secretion from alpha cells via an intra-islet paracrine mechanism[18]. It has been disputed whether GLP-1R is expressed in the alpha cells of adult islets[19,20,21,22,23,24,25,26,27], several researchers reported that GLP-1 exerts some effects through GLP-1R receptor in alpha cells[28,29], suggesting the presence of GLP-1R in Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan. It is important to manage undesirable paradoxical glucagon elevation under diabetic conditions using paracrine suppression of glucagon by insulin
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
