Insulin-like stimulation of glucose oxidation in rat adipocytes by vanadyl (IV) ions

Abstract

The mechanism of insulin action is still unknown¹. One approach to this problem is to apply substances which mimic the action of the hormone to target cells. Ouabain and deprivation of extracellular K⁺ (refs 2,3), which inhibit the active transport of Na⁺ and K⁺ ions, are both known to activate glucose transport and oxidation in isolated adipocytes. Vanadate (V) ions have recently been shown to act as very efficient inhibitors of the sodium pump or (Na⁺ + K⁺)ATPase in in vitro preparations⁴. They have a natriuretic and diuretic effect in rats⁵ and a positive inotropic effect on cat heart muscle⁶. Many tissues contain vanadium at a concentration of about 0.1–1.0 μM (ref. 7) and so endogenous vanadate could be a physiological regulator of the sodium pump. But this is still open to debate, because the bulk of the vanadium is probably in the vanadyl (IV) form^8,9 and VO²⁺ ions bind tightly to proteins^8,10. VO²⁺ is a relatively ineffective inhibitor of (Na⁺ + K⁺) ATPase in vitro^8,11. We report here that externally applied vanadate ions at low concentrations mimic fully the effect of insulin on glucose oxidation in rat adipocytes. However, this simulation seems to be due mainly to the effects of vandyl (IV) ions, probably produced within the cells, and not primarily to inhibition of the sodium pump. Also, externally applied vanadyl (IV) ions stimulate glucose oxidation substantially. Vanadyl ions are known to be powerful inhibitors of alkaline phosphatase¹² and we therefore consider the possibility that they inhibit a cellular phosphatase activity. An early event in insulin action may involve alteration of the degree of phosphorylation of protein(s) involved in regulation of sugar transport.