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Regulation of Insulin Biosynthesis

Regulation of Insulin Biosynthesis


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About the Book

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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Product Details
  • ISBN-13: 9783639135084
  • Publisher: VDM Verlag
  • Binding: Paperback
  • Language: English
  • Returnable: N
  • Spine Width: 9 mm
  • Width: 152 mm
  • ISBN-10: 3639135083
  • Publisher Date: 18 May 2010
  • Height: 229 mm
  • No of Pages: 160
  • Series Title: English
  • Weight: 295 gr


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