The signaling protein GIV/Girdin mediates the Nephrin-dependent insulin secretion of pancreatic islet β cells in response to high glucose.

ABSTRACT: Glucose-stimulated insulin secretion of pancreatic β cells is essential in maintaining glucose homeostasis. Recent evidence suggests that the Nephrin-mediated intercellular junction between β cells is implicated in the regulation of insulin secretion. However, the underlying mechanisms are only partially characterized. Herein we report that GIV is a signaling mediator coordinating glucose-stimulated Nephrin phosphorylation and endocytosis with insulin secretion. We demonstrate that GIV is expressed in mouse islets and cultured β cells. The loss of function study suggests that GIV is essential for the second phase of glucose-stimulated insulin secretion. Next, we demonstrate that GIV mediates the high glucose-stimulated tyrosine phosphorylation of GIV and Nephrin by recruiting Src kinase, w

SUBMITTER: Wang H 

PROVIDER: S-EPMC10040812 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature