Class IA phosphatidylinositol 3-kinase in pancreatic ? cells controls insulin secretion by multiple mechanisms.

ABSTRACT: Type 2 diabetes is characterized by insulin resistance and pancreatic ? cell dysfunction, the latter possibly caused by a defect in insulin signaling in ? cells. Inhibition of class IA phosphatidylinositol 3-kinase (PI3K), using a mouse model lacking the pik3r1 gene specifically in ? cells and the pik3r2 gene systemically (?DKO mouse), results in glucose intolerance and reduced insulin secretion in response to glucose. ? cells of ?DKO mice had defective exocytosis machinery due to decreased expression of soluble N-ethylmaleimide attachment protein receptor (SNARE) complex proteins and loss of cell-cell synchronization in terms of Ca(2+) influx. These defects were normalized by expression of a constitutively active form of Akt in the islets of ?DKO mice, preserving insulin secretion in response to glucose. The class IA PI3K pathway in ? cells in vivo is important in the regulation of insulin secretion and may be a therapeutic target for type 2 diabetes.

SUBMITTER: Kaneko K 

PROVIDER: S-EPMC3736578 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature