25 Scopus citations

Abstract

β-cells in the pancreatic islet respond to elevated plasma glucose by secreting insulin to maintain glucose homeostasis. In addition to glucose stimulation, insulin secretion is modulated by numerous G-protein coupled receptors (GPCRs). The GPCR ligands Kisspeptin-10 (KP) and glucagon-like peptide-1 (GLP-1) potentiate insulin secretion through Gq and Gscoupled receptors, respectively. Despite many studies, the signaling mechanisms by which KP and GLP-1 potentiate insulin release are not thoroughly understood. We investigated the downstream signaling pathways of these ligands and their affects on cellular redox potential, intracellular calcium activity ([Ca2+]i ), and insulin secretion from b-cells within intact murine islets. In contrast to previous studies performed on single b-cells, neither KP nor GLP-1 affect [Ca2 +] i upon stimulation with glucose. KP significantly increases the cellular redox potential, while no effect is observed with GLP-1, suggesting that KP and GLP-1 potentiate insulin secretion through different mechanisms. Co-treatment with KP and the Gbc-subunit inhibitor gallein inhibits insulin secretion similar to that observed with gallein alone, while co-treatment with gallein and GLP-1 does not differ from GLP-1 alone. In contrast, co-treatment with the Gbc activator mSIRK and either KP or GLP-1 stimulates insulin release similar to mSIRK alone. Neither gallein nor mSIRK alter [Ca2+]i activity in the presence of KP or GLP-1. These data suggest that KP likely alters insulin secretion through a Gbc-dependent process that stimulates glucose metabolism without altering Ca2 + activity, while GLP-1 does so, at least partly, through a Ga-dependent pathway that is independent of both metabolism and Ca2+. Experiments were performed in part through use of the Vanderbilt University Cell Imaging Shared Resource (supported by National Institutes of Health (NIH) grants P30DK020593, P30DK058404, and U24DK059637). This work was funded by NIH through grants F32DK091181 (TAS) and R01DK085064 (CAR, DWP), and by Vanderbilt University through the Louise B. McGavock Chair. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Original languageEnglish
Article numbere113020
JournalPloS one
Volume9
Issue number11
DOIs
StatePublished - Nov 17 2014

Fingerprint

Dive into the research topics of 'Differential stimulation of insulin secretion by glp-1 and kisspeptin-10'. Together they form a unique fingerprint.

Cite this