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 microM of TZDs and 100 microM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS-1 achieved at 50 microM of TZDs or 400 microM of metformin. The glucose uptake was significantly high at the combination of lower concentration (12.5 microM of TZDs and 100 microM of metformin) as compared to the combination of higher concentration (50 microM of TZDs and 400 microM 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.
Kumar
Naresh
N
Signal Transduction Research Laboratory, Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab 160 062, India.
Kaul
Chaman L
CL
Ishrath
Ansurudeen
A
Dey
Chinmoy S
CS
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D004357:Drug Synergism; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000502:physiology*; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000502:physiology; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology*
D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D045162:Thiazolidinediones; D008687:Metformin; D003847:Deoxyglucose; D011972:Receptor, Insulin; D003402:Creatine Kinase