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Background : Recent clinical studies have suggested that statins improve insulin resistance and glucose metabolism in the skeletal muscle of diabetic patients. To evaluate a possible component of this action, we measured free fatty acid oxidation in cultured human skeletal muscle cells (HSMC). Metho...

Background : Recent clinical studies have suggested that statins improve insulin resistance and glucose metabolism in the skeletal muscle of diabetic patients. To evaluate a possible component of this action, we measured free fatty acid oxidation in cultured human skeletal muscle cells (HSMC). Methods : Seven normal controls and 7 type 2 diabetic patients underwent quadriceps muscle biopsy. The HSMCs (n=14) were treated with or without lovastatin (Lova, 20 μM) for 2 days, and the free fatty acid (FFA) oxidation was measured. Results : Lova increased the oxidation of the long-chain FA palmitate to 271.2±32.7% of the control (p<0.01). Oxidation of the medium chain FA octanoate also increased after treatment of Lova (158.3±21.9%, p<0.05). One pathway of regulation of FFA is through AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation. Following Lova treatment, AMPK phosphorylation did not show a significant change while the total protein expression of AMPK was decreased (73.6±6.2% of the control, p<0.01). Lova treatment significantly increased ACC phosphorylation (149.5±20.6% of the control, p<0.05). Conclusion : Lova increased FFA oxidation by increasing the ACC phosphorylation in human skeletal muscle cells. Stimulation of skeletal muscle FFA oxidation may be one mechanism by which statins act to lower intramyocellular triglyceride and improve insulin action on glucose metabolism.

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