The mechanism of the insulin-like effects of ionic zinc.

The insulin-like effects of ionic zinc (Zn2+) were studied in isolated rat adipocytes. Concentrations of Zn2+ between 250 and 1000 microM stimulated 3-O-methylglucose transport and glucose metabolism to CO2, glyceride-fatty acid, and glyceride-glycerol. Selective stimulation of the pentose phosphate cycle was observed since a Zn2+-induced increase in glucose carbon 1 oxidation persisted even when glucose transport was blocked with 50 microM cytochalasin B or when transport was no longer rate-limiting for metabolism at high concentrations of glucose. Enhanced pentose phosphate cycle activity may have been due to a selective inhibition of glutathione reductase by the ion, which was also accompanied by a fall in cellular glutathione content. Zn2+ also inhibited lipolysis stimulated by the beta-adrenergic agent ritodrine in the absence of glucose. The effects of Zn2+ on glucose oxidation and stimulated rates of lipolysis were inhibited by extracellular catalase, indicating that they were largely a result of H2O2 generation. The H2O2 production appeared for the most part to be caused by zinc-catalyzed autoxidation of sulfhydryl groups present on external cell membranes, although involvement of sulfhydryl groups on bovine serum albumin in the buffer could also have contributed. The insulin-like effects of Zn2+ in adipocytes are therefore caused not only by direct effects of the ion on intracellular metabolism but also by indirect effects related to H2O2 generation.