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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Free fatty acid-induced muscle insulin resistance and glucose uptake dysfunction: Evidence for PKC activation and oxidative stress-activated signaling pathways
Biochemical and Biophysical Research Communications, Volume 389, No. 2, Year 2009
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Description
In the present study, we examined the effects of free fatty acids (FFAs) on insulin sensitivity and signaling cascades in the C2C12 skeletal muscle cell culture system. Our data clearly manifested that the inhibitory effects of PKC on insulin signaling may at least in part be explained by the serine/threonine phosphorylation of IRS-1. Both oleate and palmitate treatment were able to increase the Serine307 phosphorylation of IRS-1. IRS-1 Serine307 phosphorylation is inducible which causes the inhibition of IRS-1 tyrosine phosphorylation by either IκB-kinase (IKK) or c-jun N-terminal kinase (JNK) as seen in our proteomic kinases screen. Furthermore, our proteomic data have also manifested that the two FFAs activate the IKKα/β, the stress kinases S6 kinase p70 (p70SK), stress-activated protein kinase (SAPK), JNK, as well as p38 MAP kinase (p38MAPK). On the other hand, the antioxidant, Taurine at 10 mM concentrations was capable of reversing the oleate-induced insulin resistance in myocytes as manifested from the glucose uptake data. Our current data point out the importance of FFA-induced insulin resistance via multiple signaling mechanisms. Crown Copyright © 2009.
Authors & Co-Authors
Ragheb, Rafik
Egypt, Cairo
College of Science
Canada, Toronto
University Health Network University of Toronto
Canada, Toronto
Hospital for Sick Children University of Toronto
Canada, Toronto
Mount Sinai Hospital of University of Toronto
Canada, Toronto
University of Toronto
SHANAB, Gamila M.L.
Egypt, Cairo
College of Science
Medhat, A. M.
Egypt, Cairo
College of Science
Seoudi, Dina M.
Egypt, Cairo
College of Science
Adeli, Khosrow
Canada, Toronto
Hospital for Sick Children University of Toronto
Canada, Toronto
University of Toronto
Fantus, Ivan George
Canada, Toronto
University Health Network University of Toronto
Canada, Toronto
Mount Sinai Hospital of University of Toronto
Canada, Toronto
University of Toronto
Statistics
Citations: 110
Authors: 6
Affiliations: 5
Identifiers
Doi:
10.1016/j.bbrc.2009.08.106
ISSN:
0006291X
e-ISSN:
10902104