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Regulation of Insulin Biosynthesis

Regulation of Insulin Biosynthesis

Paperback

Biology

Currently unavailable to order

ISBN10: 3639135083
ISBN13: 9783639135084
Publisher: Blues Kids Of Amer
Published: May 18 2010
Pages: 160
Weight: 0.54
Height: 0.37 Width: 6.00 Depth: 9.00
Language: English
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 glucosestimulated 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.

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Biology