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

Cell Metab. 2010 Dec 1;12(6):619-32. doi: 10.1016/j.cmet.2010.11.005.


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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Class Ia Phosphatidylinositol 3-Kinase / genetics
  • Class Ia Phosphatidylinositol 3-Kinase / metabolism*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Exocytosis / physiology
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / enzymology*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Mice
  • Mice, Knockout
  • Reverse Transcriptase Polymerase Chain Reaction
  • SNARE Proteins / metabolism


  • Insulin
  • SNARE Proteins
  • Class Ia Phosphatidylinositol 3-Kinase