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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/18962

Title: Insulin Sensitivity is Enhanced by CGMP-mediated MAPK Inhibition in Rat Adipocytes
Authors: Thomas, Garry
Advisor: Fantus, I. George
Department: Physiology
Keywords: ANP
insulin resistance
bradykinin
diabetes
MAPK
AKT
PKB
cGMP
PKG
Issue Date: 16-Feb-2010
Abstract: Bradykinin (BK) acts through eNOS to reduce MAPK-mediated feedback inhibition of insulin signalling. Preliminary data suggest that the sGC-cGMP-PKG pathway, a prominent NO target, is involved. Our present study aimed to support the role of this pathway with atrial natriuretic peptide (ANP), which uses a receptor associated GC (NPR-A) to generate cGMP. We found that treating adipocytes with ANP mimicked BK effects on insulin-stimulated glucose uptake, Tyr-IRS-1 and Akt/PKB phosphorylation, as well as JNK and ERK1/2 inhibition. These outcomes depended on GC-cGMP-PKG signalling since A71915 (NPR-A antagonist), and KT-5823 (PKG inhibitor), completely abrogated them, while zaprinast (phosphodiesterase inhibitor), prolonged ANP actions. Furthermore, decreased MAPK phosphorylation was independent of upstream kinase activity, suggesting that MAPK phosphatases may be involved. These data indicate that BK and ANP act through the GC-cGMP-PKG pathway to potentiate insulin signalling via attenuated feedback inhibition. Stimulating the GC-cGMP-PKG pathway may, therefore, be a promising therapy for T2DM.
URI: http://hdl.handle.net/1807/18962
Appears in Collections:Master
Department of Physiology - Master theses

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