title: Chromium (D-phenylalanine)3 supplementation alters glucose disposal, insulin signaling, and glucose transporter-4 membrane translocation in insulin-resistant mice.
abstract: 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 mug.kg(-1).d(-1) ( approximately 3.8 mug 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.
authors.affiliation: University of Wyoming, School of Pharmacy, Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, Laramie, WY 82071, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Dong
authors.forename: Machender Reddy
authors.initials: MR
authors.lastname: Kandadi
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.forename: Nair
authors.initials: N
authors.lastname: Sreejayan
mesh_terms: D000821:Animal Feed; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D019587:Dietary Supplements; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D007333:Insulin Resistance; D051379:Mice; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D009124:Muscle Proteins; D009942:Organometallic Compounds; C512471:chromium (D-Phenylalanine)3; D010649:Phenylalanine; D003847:Deoxyglucose