Details

Autor(en) / Beteiligte

• Zhang, Sharon S
• Hao, Ergeng
• Yu, Jianxiu
• Liu, Wen
• Wang, Jing
• Levine, Fred
• Feng, Gen-Sheng

Titel

Coordinated regulation by Shp2 tyrosine phosphatase of signaling events controlling insulin biosynthesis in pancreatic [beta]-cells

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2009-05, Vol.106 (18), p.7531

Ort / Verlag

Washington: National Academy of Sciences

Erscheinungsjahr

2009

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Intracellular signaling by which pancreatic β-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 β-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 β-cells. Therefore, Shp2 acts as a signal coordinator in β-cells, orchestrating multiple pathways controlling insulin biosynthesis to maintain glucose homeostasis. [PUBLICATION ABSTRACT]