| First Author | Kaneko K | Year | 2010 |
| Journal | Cell Metab | Volume | 12 |
| Issue | 6 | Pages | 619-32 |
| PubMed ID | 21109194 | Mgi Jnum | J:168115 |
| Mgi Id | MGI:4881891 | Doi | 10.1016/j.cmet.2010.11.005 |
| Citation | Kaneko K, et al. (2010) Class IA phosphatidylinositol 3-kinase in pancreatic beta cells controls insulin secretion by multiple mechanisms. Cell Metab 12(6):619-32 |
| abstractText | Type 2 diabetes is characterized by insulin resistance and pancreatic beta cell dysfunction, the latter possibly caused by a defect in insulin signaling in beta cells. Inhibition of class IA phosphatidylinositol 3-kinase (PI3K), using a mouse model lacking the pik3r1 gene specifically in beta cells and the pik3r2 gene systemically (betaDKO mouse), results in glucose intolerance and reduced insulin secretion in response to glucose. beta cells of betaDKO 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 betaDKO mice, preserving insulin secretion in response to glucose. The class IA PI3K pathway in beta cells in vivo is important in the regulation of insulin secretion and may be a therapeutic target for type 2 diabetes. |
