Mechanisms of Fatty Acid-Induced Insulin Resistance in Muscle and LiverRafik Ragheb1,2,3,4,5* and Amina M. Medhat1
1University of Ain Shams – Department of Biochemistry – Faculty of Science, Cairo – Egypt
2University Health Network, Canada
3Hospital for Sick Children, Canada
4Mount Sinai Hospital, Canada
5University of Toronto, Toronto, Canada
- Corresponding Author:
- Rafik Ragheb
University of Toronto, Toronto – Canada
E-mail: [email protected]
Received Date: April 06, 2011; Accepted Date: May 13, 2011; Published Date: May 16, 2011
Citation: Ragheb R, Medhat AM (2011) Mechanisms of Fatty Acid-Induced Insulin Resistance in Muscle and Liver. J Diabetes Metab 2:127. doi:10.4172/2155-6156.1000127
Copyright: © 2011 Ragheb R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Insulin Resistance occurs as a result of disturbances in lipid metabolism and increased levels of circulating fatty acids that accumulate within the insulin sensitive tissues such as muscle, liver and adipose tissues. Increased fatty acid flux has been suggested to be strongly associated with insulin resistant states such as obesity and type 2-diabetes. Fatty acids appear to cause this defect in glucose transport by inhibiting insulin -stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and reducing IRS-1 associated phosphatidyl-inositol 3-kinase activity that implicate other insulin signaling components downstream of the insulin signaling cascade. A number of different metabolic abnormalities may increase intramyocellular or intrahepatic fatty acid metabolites that induce the disease state of insulin resistance through a number of different cellular mechanisms. The current review point out the link between enhanced FFA flux and activation of PKC and how it impacts on both the insulin signaling in muscle and liver.