Vanadate increases cell surface insulin binding and improves insulin sensitivity in both normal and insulin-resistant rat adipocytes.

Abstract

The aim of this study was to elucidate the acute effects of vanadate on cell surface insulin binding and insulin sensitivity in rat adipocytes. The cells were preincubated at 37 degrees for 20 min followed by energy depletion with potassium cyanide, extensive washing and 125I-insulin binding. The presence of vanadate or insulin during the preincubation period dose-dependently enhanced 125I-insulin binding to normal adipocytes (maximally 4-5-fold) through an increased number of binding sites without any change in receptor affinity. Submaximal concentrations of vanadate added together with insulin enhanced the cellular sensitivity to the effect of insulin to stimulate 3-O-methylglucose transport. Vanadate, but not insulin, was also capable of increasing insulin binding as well as insulin sensitivity in insulin-resistant cells (treatment with N6-monobutyryl cAMP or amiloride and adipocytes from obese, aging rats). There was a correlation between the effect of vanadate to augment insulin binding and its ability to enhance cellular insulin sensitivity. Thus, the data suggest that short-term vanadate treatment improves insulin sensitivity through enhanced receptor binding and that this occurs in both normal and insulin-resistant cells.