Magnesium deficiency modulates the insulin signaling pathway in liver but not muscle of rats

Altered insulin secretion and sensitivity have been observed in Mg-deficien t animals. However, the effects of Mg deficiency and supplementation on int racellular signaling events triggered by insulin are unknown. Therefore, we studied the early steps of insulin action in muscle and liver of rats fed Mg-deficient (DF-6, DF-11) or control (CO-6, CO-11) diets for 6 or 11 wk, r espectively, and Mg-deficient or control diets for 6 wk, followed by Mg sup plementation for 5 wk (SDF and SCO groups, respectively). There were no dif ferences in the glucose disappearance rate (K-itt) or insulin signaling bet ween CO-6 and DF-6 rats. Between the two groups of rats fed for 11 wk, the DF-11 group had a significantly greater K-itt. SDF and SCO rats had K-itt t hat did not differ from CO-11 rats, but that were significantly lower than in DF-11 rats. In the latter rats, insulin receptor and insulin receptor su bstrate-1 protein and phosphorylation levels were elevated in liver and the re was a greater association between the insulin receptor substrate-1 and p 85 subunit of phosphatidylinositol 3-kinase compared with CO-11 rats. There were no differences in the early steps of insulin action in SDF and contro l rats. These results suggest that the normal insulin sensitivity maintaine d by Mg supplementation and the increased insulin sensitivity produced by a long period of Mg deprivation may result, at least in part, from alteratio ns in or maintenance of the early molecular steps of insulin action in hepa tic tissue.