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 muM of TZDs and 100 muM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS-1 achieved at 50 muM of TZDs or 400 muM of metformin. The glucose uptake was significantly high at the combination of lower concentration (12.5 muM of TZDs and 100 muM of metformin) as compared to the combination of higher concentration (50 muM of TZDs and 400 muM 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. (C) 2003 Elsevier Inc. All rights reserved.