Glucagon-like peptide-1 receptor-mediated endosomal cAMP generation promotes glucose-stimulated insulin secretion in pancreatic β-cells

Kuna, Ramya S. ; Girada, Shravan Babu ; Asalla, Suman ; Vallentyne, Joyprashant ; Maddika, Subbareddy ; Patterson, James T. ; Smiley, David L. ; DiMarchi, Richard D. ; Mitra, Prasenjit (2013) Glucagon-like peptide-1 receptor-mediated endosomal cAMP generation promotes glucose-stimulated insulin secretion in pancreatic β-cells American Journal of Physiology: Endocrinology and Metabolism, 305 (2). E161-E170. ISSN 0193-1849

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Official URL: http://doi.org/10.1152/ajpendo.00551.2012

Related URL: http://dx.doi.org/10.1152/ajpendo.00551.2012

Abstract

Glucagon-like peptide-1 receptor (GLP-1R) plays a major role in promoting glucose-stimulated insulin secretion in pancreatic β-cells. In the present study, we synthesized a novel functional analog of GLP-1 conjugated to tetramethyl rhodamine to monitor the internalization of the receptor. Our data show that after being internalized the receptor is sorted to lysosomes. In endosomes, receptor-ligand complex is found to be colocalized with adenylate cyclase. Pharmacological inhibition of endocytosis attenuates GLP-1R-mediated cAMP generation and consequent downstream protein kinase A substrate phosphorylation and glucose-stimulated insulin secretion. Our study underlines a paradigm shift in GLP-1R signaling and trafficking. The receptor ligand complex triggers cAMP generation both in plasma membrane and in endosomes, which has implications for receptor-mediated regulation of insulin secretion.

Item Type:Article
Source:Copyright of this article belongs to American Physical Society.
ID Code:118525
Deposited On:23 May 2021 19:05
Last Modified:23 May 2021 19:05

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