Differential Stimulation of Insulin Secretion by GLP
These data suggest that KP likely alters insulin secretion through a G βγ -dependent process that stimulates glucose metabolism without altering Ca 2+ activity, while GLP-1 does so, at least partly, through a G α -dependent pathway that is independent of both metabolism and Ca 2+.
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 β-cells within intact murine islets.
Differential stimulation of insulin secretion by GLP
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 ( [Ca (2+)]i), and insulin secretion from β-cells within intact murine ...
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+.
(PDF) Differential Stimulation of Insulin Secretion by GLP
These data suggest that KP likely alters insulin secretion through a Gβγ-dependent process that stimulates glucose metabolism without altering Ca2+ activity, while GLP-1 does so, at least partly ...
Abstract Stimulation of insulin secretion by glucagon-like peptide-1 ( GLP-1 ) and other gut-derived peptides is central to the incretin response to ingesting nutriments. Analogues of GLP-1 , and inhibitors of its breakdown, have found widespread clinical use for the treatment of type 2 diabetes (T2D) and obesity.
Overview of Differential Stimulation Of Insulin Secretion By Glp 1
GLP-1 and its analogs enhance insulin secretion , but the specific intracellular mechanisms in β-cells remain unclear. Key intracellular mediators including calcium, glutamate, γ-aminobutyric acid, serotonin, and urocortin-3 are modulated by GLP-1 signaling with variable and sometimes contradictory effects.
Both GLP-1 and glucose participated in regulating every single step of the secretion pathway, and systematically synergized their effects in inducing insulin secretion .
Systematic Synergy of Glucose and GLP
Finally, we found glucose and GLP-1 executed their synergistic effect at multiple levels, especially at pathway level. Both GLP-1 and glucose participated in regulating every single step of the secretion pathway, and systematically synergized their effects in inducing insulin secretion .
Lindquist et al. show that GLP-1 and semaglutide, but not exendin 4 or GIP, selectively drive GLP -1R-GIPR heterodimerization, altering receptor trafficking and signaling. These findings uncover a mechanistic basis for incretin crosstalk and provide a structural framework for optimizing therapies for obesity and type 2 diabetes.