jdm

Journal of Diabetes & Metabolism

ISSN - 2155-6156

Abstract

Mechanisms of Fatty Acid-Induced Insulin Resistance in Muscle and Liver

Rafik Ragheb and Amina M. Medhat

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.

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