| First Author | Zhang SS | Year | 2009 |
| Journal | Proc Natl Acad Sci U S A | Volume | 106 |
| Issue | 18 | Pages | 7531-6 |
| PubMed ID | 19380737 | Mgi Jnum | J:148327 |
| Mgi Id | MGI:3844369 | Doi | 10.1073/pnas.0811715106 |
| Citation | Zhang SS, et al. (2009) Coordinated regulation by Shp2 tyrosine phosphatase of signaling events controlling insulin biosynthesis in pancreatic beta-cells. Proc Natl Acad Sci U S A 106(18):7531-6 |
| abstractText | Intracellular signaling by which pancreatic beta-cells synthesize and secrete insulin in control of glucose homeostasis is not fully understood. Here we show that Shp2, a cytoplasmic tyrosine phosphatase possessing 2 SH2 domains, coordinates signaling events required for insulin biosynthesis in beta-cells. Mice with conditional ablation of the Shp2/Ptpn11 gene in the pancreas exhibited defective glucose-stimulated insulin secretion and impaired glucose tolerance. Consistently, siRNA-mediated Shp2-knockdown in rat insulinoma INS-1 832/13 cells resulted in decreased insulin production and secretion despite an increase in cellular ATP. Shp2 modulates the strength of signals flowing through Akt/FoxO1 and Erk pathways, culminating in control of Pdx1 expression and activity on Ins1 and Ins2 promoters, and forced Pdx1 expression rescued insulin production in Shp2-knockdown beta-cells. Therefore, Shp2 acts as a signal coordinator in beta-cells, orchestrating multiple pathways controlling insulin biosynthesis to maintain glucose homeostasis. |
