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Biochemical, Molecular, and Genetic Mechanisms

Chromium (D-phenylalanine)₃ Supplementation Alters Glucose Disposal, Insulin Signaling, and Glucose Transporter-4 Membrane Translocation in Insulin-Resistant Mice^1–3,

University of Wyoming, School of Pharmacy, Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, Laramie, WY 82071 and ⁵ Department of Pharmaceutical Sciences, Manipal University, Manipal, India

^* To whom correspondence should be addressed. E-mail: sreejay{at}uwyo.edu.

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.