Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC224
Effects of chronic insulin and saturated fatty acid exposure on mitochondrial function in cultured myocytes.
C. Yang1, C. Aye1, X. Li1, A. Diaz Ramos2, A. Zorzano2, S. Mora1
1. Physiology, University of Liverpool, Liverpool, United Kingdom. 2. IRB, Barcelona, Spain.
Mitochondrial dysfunction has been associated with insulin resistance, obesity and diabetes. However, whether mitochondrial dysfunction is the consequence or cause of insulin resistance is controversial. Insulin signalling has been shown to regulate expression of mitochondrial genes. Here we examined the independent contributions of impaired insulin signalling and saturated fatty acid exposure on mitochondrial function and gene expression in cultured myocytes. Chronic insulin treatment of myotubes resulted in insulin resistance, with reduced signalling through Phosphatidyl inositol 3-Kinase/AKT signaling pathway. Insulin-resistant myocytes exhibited lower mitochondrial membrane potential and ROS production but comparable ATP production to control cells. The activity of the mitochondrial marker citrate synthase was increased in insulin-resistant cells compared to controls. The expression of a number of mitochondrial genes including COX1, COX2, COX4, ATP synthase, Tfam, NRF1, Mitofusin 2, and porin were also largely unaffected by chronic insulin exposure. However, the transcriptional co-activator PGC1α, and uncoupling proteins, UCP2 and UCP3 were significantly reduced in this insulin resistant cell model. In contrast, treatment of cells with saturated fatty acid reduced mitochondrial membrane potential but significantly increased ROS production, and increased the mRNA expression of UCP2, UCP3 and ATP synthase. These cells also displayed lower levels PGC1α and PGC1β gene expression compared to controls. Taken together these results suggest that chronic hyperinsulinemia causes insulin resistance but not mitochondrial dysfunction. However, insulin fails to protect against fatty acid-induced mitochondrial dysfunction.
Where applicable, experiments conform with Society ethical requirements