Mechanism by Which Fatty Acids Inhibit Insulin Activation of Insulin Receptor Substrate-1 (IRS-1)-associated Phosphatidylinositol 3-Kinase Activity in Muscle
Howard Hughes Medical Institute · Joslin Diabetes Center · +5 more institutions
Abstract
Recent studies have demonstrated that fatty acids induce insulin resistance in skeletal muscle by blocking insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-kinase). To examine the mechanism by which fatty acids mediate this effect, rats were infused with either a lipid emulsion (consisting mostly of 18:2 fatty acids) or glycerol. Intracellular C18:2 CoA increased in a time-dependent fashion, reaching an approximately 6-fold elevation by 5 h, whereas there was no change in the concentration of any other fatty acyl-CoAs. Diacylglycerol (DAG) also increased transiently after 3-4 h of lipid infusion. In contrast there was no increase in intracellular ceramide…
Citation impact
- FWCI
- 22.80
- Percentile
- 100%
- References
- 21
Authors
14- CYChunli YuCorresponding
- YCYan Chen
Howard Hughes Medical Institute, Joslin Diabetes Center, Yale University
- GWGary W. Cline
Joslin Diabetes Center, Howard Hughes Medical Institute, University of New Haven
- DZDongyan Zhang
Howard Hughes Medical Institute, Joslin Diabetes Center, Yale University
- HZHaihong Zong
University of New Haven, Howard Hughes Medical Institute, Joslin Diabetes Center
Topics & keywords
- Insulin receptor
- Internal medicine
- Endocrinology
- Diacylglycerol kinase
- IRS1
- Phosphatidylinositol
- Insulin resistance
- Insulin receptor substrate