Effect of chromium and zinc on insulin signaling in skeletal muscle cells.
Patients on total parenteral nutrition without Cr supplementation develop symptoms similar to those of diabetes. Zn has been implicated in diabetes because of its antioxidant properties and interaction with insulin. To study the effect of these metal ions on insulin signaling proteins, cultured mouse skeletal muscle cells was used as an in vitro model, as the tissue accounts for more than 80% of insulin-stimulated glucose disposal in the body. In the present study, it has been observed that both Cr and Zn, upon prolonged exposure, could stimulate tyrosine phosphorylation of insulin receptor (IR) even in the absence of insulin. Insulin-mediated IR tyrosine phosphorylation was enhanced by the treatment with both of the metal ions. Both Cr and Zn could phosphorylate insulin receptor substrate-1 (IRS-1). Phosphorylation of IRS-1 induced by metal ions was higher than that induced by insulin. Hence, both Cr and Zn were found to have insulin mimetic activity. Both of the metal ions were also found to potentiate insulin-mediated activation of IRS-1. The basal level of glucose uptake was also increased by prolonged treatment of the cells with the metal ions. The ions could also enhance the insulin-stimulated glucose uptake into the cells. Therefore, both Zn and Cr seem to have a positive effect on insulin signaling leading to glucose uptake.
Miranda
Edward Roshan
ER
Signal Transduction Research Laboratory, Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab 160 062, India.
Dey
Chinmoy Sankar
CS
D000818:Animals; D002460:Cell Line; D002857:Chromium / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D002857:Chromium; D014443:Tyrosine; D003847:Deoxyglucose; D048051:p38 Mitogen-Activated Protein Kinases; D015032:Zinc