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Kuna, R.S. and Girada, S.B. and Asalla, S. and Vallentyne, J. and Subba Reddy, Maddika and Patterson, J.T. and Smiley, D.L. and DiMarchi, R.D. and Mitra, P. (2013) Glucagon-like peptide-1 receptor-mediated endosomal cAMP generation promotes glucose-stimulated insulin secretion in pancreatic -cells. American Journal of Physiology - Endocrinology and Metabolism, 305 (2). E161-E170. ISSN 0193-1849

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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
Additional Information: [Open Access from the Publisher]
Depositing User: Dr P Divakar
Date Deposited: 26 Nov 2015 06:57
Last Modified: 26 Nov 2015 06:57
URI: http://cdfd.sciencecentral.in/id/eprint/678

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