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Regulation of Insulin Biosynthesis

Sharon S. Zhang

ISBN 10: 3639135083 / ISBN 13: 9783639135084
Published by VDM Verlag
New Condition: New Soft cover
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160 pages. Dimensions: 8.7in. x 5.9in. x 0.4in.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 Shp2Ptpn11 gene in the pancreas exhibited defective glucosestimulated insulin secretion and impaired glucose tolerance. Consistently, siRNA-mediated Shp2-knockdown in rat insulinoma INS-1 83213 cells resulted in decreased insulin production and secretion despite an increase in cellular ATP. Shp2 modulates the strength of signals flowing through AktFoxO1 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. This item ships from multiple locations. Your book may arrive from Roseburg,OR, La Vergne,TN. Bookseller Inventory # 9783639135084

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Bibliographic Details

Title: Regulation of Insulin Biosynthesis

Publisher: VDM Verlag

Binding: Paperback

Book Condition:New

Book Type: Paperback

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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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