| Objective: Curcumin is a natural polyphenol compound. Curcumin has beenreported to lower plasma lipids and glucose and to increase glucose homeostasis intype2diabetic animals. Muscular insulin resistance is an important feature of type2diabetes. However, it is unclear whether curcumin can improve muscular insulinresistance. We conducted the present study to determine the effect of curcumin onmuscular insulin resistance as well as the mechanism by looking into its effects onlipid and glucose metabolism in skeletal muscle of type2diabetic rats and L6insulin-resistant myotubes.Methods: In vivo experiment:100male wistar rats were divided into two groups,10were used as control, the other90were used to develop type2diabetes by lowdose STZ (30mg/kg) injection intraperitoneally combined with high fat diet. Afterdiabetic model established, the diabetic rats were divided into diabetic group, low(50mg/kg BW), medium (150mg/kg BW) and high (250mg/kg BW) doses ofcurcumin intervention groups. Curcumin intervention lasted for45days. Fastingblood glucose, lipids, serum insulin were measured; enzymes involve in fatty acidsand glucose metabolism in skeletal muscle were detected by Western blot. In vitroexperiment: L6myotubes were divided into control group, insulin resistant group andcurcumin treatment groups. Myotubes in control group were normal. Myotubes ininsulin resistant group were incubated with0.25mmol/L palmitate for24h. Myotubesin curcumin treatment groups were incubated with5μmol/L,10μmol/L,20μmol/L and40μmol/L curcumin in the presence of0.25mmol/L palmitate for24h. Glucose uptake by myotubes was measured using2-deoxy-[3H] D-glucose; palmitate concentration intne medium was determined by GS-MS; the expression of proteins regulating glucoseand fatty acids metabolism were detected by Western blot.Results: In vivo experiment: curcumin significantly decreased blood glucose,lipids, serum FFAs and increased serum insulin; curcumin up-regulated expression ofphosphorylated AMPK, membrane FAT/CD36, mitochondrial CPT1and MCAD, butdown-regulated expression of PDK4and phosphorylated GS. In vitro experiment:curcumin at10μmol/L was adequate to cause a significant increase in2-deoxy-[3H]D-glucose uptake by L6myotubes; palmitate concentration in themedium of curcumin-treated L6myotubes was lower than that of insulin-resistantmyotubes; curcumin up-regulated expression of phosphorylated LKB1,phosphorylated AMPK, phosphorylated ACC, PPARα, CPT1, MCAD, FAT/CD36andGLUT4, but down-regulated expression of PDK4and phosphorylated GS ininsulin-resistant L6myotubes; the effects of curcumin on AMPK and downstreammolecules were suppressed by AMPK inhibitor, Compound C; LKB1, an upstreamkinase of AMPK, was activated by curcumin and inhibited together with AMPK anddownstream molecules by radicicol, an LKB1destabilizer.Conclusion: Curcumin lowers blood glucose, lipids and imprvoes insulinsensitivity in type2diabetic rats; curcumin enhances glucose oxidation and glycogensynthesis in insulin-resistant skeletal muscle; curcumin increases fatty acids βoxidation and inhibits lipids accumulation in insulin-resistant skeletal muscle;curcumin plays its anti-insulin resistance role, at least in part, through LKB1-AMPKpathway. |
