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.
D019325:3-O-Methylglucose; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003571:Cytochalasin B / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects; D008757:Methylglucosides / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
D007328:Insulin; D008757:Methylglucosides; D013481:Superoxides; D019325:3-O-Methylglucose; D003571:Cytochalasin B; D006861:Hydrogen Peroxide; D005978:Glutathione; D005947:Glucose; D015032:Zinc