Chromium (d-phenylalanine)3 Supplementation Alters Glucose Disposal, Insulin Signaling, and Glucose Transporter-4 Membrane Translocation in Insulin-Resistant Mice

摘要

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 (S group) or to receive oral Cr(D-phe)3 in drinking water (SCr group) at a dose of 45 μg·kg?1·d?1 (～3.8 μg of elemental chromium·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.