Chromium(D-phenylalanine)(3) supplementation alters glucose disposal, insulin signaling, and glucose transporter-4 membrane translocation in insulin-resistant mice

Chromium has gained popularity as a nutritional supplement for diabetic and insulin-resistant subjects. This study was designed to evaluate the effect of chronic administration of a novel chromium complex Of D-phenylalanine [Cr(D-phe)(3)]in insulin-resistant, sucrose-fed mice. Whole-body insulin resistance was generated in FVB mice by 9 wk of sucrose feeding, following which they were randomly assigned to be unsupplemented IS group) or to receive oral Cr(D-phe)3 in drinking water (SCr group) at a dose of 45 mu g.kg(-1).d(-1) (similar to 3.8 mu g of elemental chrornium.kg(-1).d(-1)). A control group (C) did not consume sucrose and was not supplemented. Sucrose-fed mice had an elevated serum insulin concentration compared with controls and this was significantly lower in sucrose-fed mice that received Cr(D-phe)3, which did not differ from controls. Impaired glucose tolerance in sucrose-fed mice, evidenced by the poor glucose disposal rate following an intraperitoneal glucose tolerance test, was significantly improved in mice receiving Cr(D-phe)(3). Chromium supplementation significantly enhanced insulin-stimulated Akt phosphorylation and membrane-associated glucose transporter-4 in skeletal muscles of sucrose-fed mice. In cultured adipocytes rendered insulin resistant by chronic exposure to high concentrations of glucose and insulin, Cr(D-phe)(3) augmented Akt phosphorylation and glucose uptake. These results indicate that dietary supplementation with Cr(D-phe)3 may have potential beneficial effects in insulin-resistant, prediabetic conditions.