Class IA phosphatidylinositol 3-kinase in pancreatic β cells controls insulin secretion by multiple mechanisms Academic Article uri icon

Overview

MeSH Major

  • Class Ia Phosphatidylinositol 3-Kinase
  • Diabetes Mellitus, Type 2
  • Insulin
  • Insulin-Secreting Cells

abstract

  • Type 2 diabetes is characterized by insulin resistance and pancreatic β cell dysfunction, the latter possibly caused by a defect in insulin signaling in β cells. Inhibition of class IA phosphatidylinositol 3-kinase (PI3K), using a mouse model lacking the pik3r1 gene specifically in β cells and the pik3r2 gene systemically (βDKO mouse), results in glucose intolerance and reduced insulin secretion in response to glucose. β cells of βDKO 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 βDKO mice, preserving insulin secretion in response to glucose. The class IA PI3K pathway in β cells in vivo is important in the regulation of insulin secretion and may be a therapeutic target for type 2 diabetes.

publication date

  • December 2010

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3736578

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2010.11.005

PubMed ID

  • 21109194

Additional Document Info

start page

  • 619

end page

  • 32

volume

  • 12

number

  • 6