Combination of metformin and thiazolidindiones restore insulin signalling in insulin-resistant cultured myotubes

We examined the effect of combination of thiazolidinediones (TZDs) and metformin on insulin-resistant skeletal muscle cells. The combined use of TZDs and metformin resulted in maximum tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) at 12.5 μM of TZDs and 100 μM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS-1 achieved at 50 μM of TZDs or 400 μM of metformin. The glucose uptake was significantly high at the combination of lower concentration (12.5 μM of TZDs and 100 μM of metformin) as compared to the combination of higher concentration (50 μM of TZDs and 400 μM of metformin). Results demonstrated that (1) Additive effect on insulin sensitization can be achieved by a combination of TZDs and metformin at lower concentration; (2) combination of TZDs and metformin act on insulin signaling molecules in insulin resistance; (3) in vitro system has the potentiality to determine possible target molecule(s) and mechanism of action of drugs.