Zinc has an insulin-like effect on glucose transport mediated by phosphoinositol-3-kinase and AKT in 3T3-L1 fibroblasts and adipocytes

Zinc has insulin-like effects on cells, including promotion of both lipogen esis and glucose transport. The relationship between zinc and the stimulati on of glucose transport is unclear. We hypothesize that zinc affects the in sulin-signaling pathway. In this study, the effect of zinc on glucose trans port and insulin signaling was examined in 3T3-L1 -preadipocytes and -adipo cytes. Treatment of cells with up to 200 mu mol/L zinc significantly increa sed glucose transport (P < 0.05), The effect of zinc on adipocytes was grea ter than on preadipocytes, and the effect of zinc plus insulin was greater than that of either insulin or zinc alone. Cytochalasin D, which disrupts a ctin filaments, attenuated the increase of glucose transport induced by zin c or insulin (P < 0.05). At 100 nmol/L, wortmannin, the phosphoinositide (P I) 3-kinase inhibitor, decreased basal glucose transport and blocked zinc-s timulated glucose transport in both cell types (P < 0.05). H7, an inhibitor of protein kinase C, did not reduce basal glucose transport but decreased zinc-induced glucose transport (P < 0.05), Zinc increased tyrosine phosphor ylation of the insulin receptor p subunit of both preadipocytes and adipocy tes after 5-10 min of treatment (P < 0.05). Zinc at 200 mu mol/L did not af fect tyrosine phosphorylation of insulin receptor substrate (IRS)-1 or -2; further, there was no effect of zinc on the association of the p85 subunit of PI 3-kinase and IRS-1, Zinc significantly increased serine-473 phosphory lation of Akt in both preadipocytes and adipocytes (P < 0.05). The PI 3-kin ase inhibitor, wortmannin, totally blocked the effect of zinc on Akt activa tion. Hence, it appears that zinc can induce an increase in glucose transpo rt into cells and potentiate insulin-induced glucose transport, likely acti ng through the insulin-signaling pathway.