Curcumin improves insulin resistance in skeletal muscle of rats

Background and aims: Curcumin has been reported to lower plasma lipids and glucose in diabetic rats, and to decrease body weight in obese rats, which may partly be due to increased fatty acid oxidation and utilization in skeletal muscle. Methods and results: Diabetic rats induced by high-fat diet plus streptozotocin (STZ, 30 mg/kg BW) were fed a diet containing 50, 150, or 250 mg/kg BW curcumin for 7 wk. Curcumin dose-dependently decreased plasma lipids and glucose and the dose 150 mg/kg BW appeared to be adequate to produce a significant effect. Curcumin supplementation reduced glucose and insulin tolerance measured as areas under the curve. L6 myotubes were treated with palmitate (0.25 mmol/L) in the presence of different levels of curcumin for 24 h in our in vitro experiment. Curcumin at 10 mmol/L was adequate to cause a significant increase in 2-deoxy-[(3)H]D-glucose uptake by L6 myotubes. Curcumin up-regulated expression of phosphorylated AMP-activated protein kinase (AMPK), CD36, and carnitine palmitoyl transferase 1, but down-regulated expression of pyruvate dehydrogenase 4 and phosphorylated glycogen synthase (GS) in both in vivo and in vitro studies. Moreover, curcumin increased phosphorylated acetyl COA carboxylase in L6 myotubes. The effects of curcumin on these enzymes except for GS were suppressed by AMPK inhibitor, Compound C. LKB1, an upstream kinase of AMPK, was activated by curcumin and inhibited by radicicol, an LKB1 destabilizer. Conclusion: Curcumin improves muscular insulin resistance by increasing oxidation of fatty acid and glucose, which is, at least in part, mediated through LKB1-AMPK pathway. (C) 2009 Elsevier B. V. All rights reserved.