Chromium (D-phenylalanine)3 alleviates high fat-induced insulin resistance and lipid abnormalities.
High-fat diet has been implicated as a major cause of insulin resistance and dyslipidemia. The objective of this study was to evaluate the impact of dietary-supplementation of chromium (D-phenylalanine)(3) [Cr(D-Phe)(3)] on glucose and insulin tolerance in high-fat diet fed mice. C57BL/6-mice were randomly assigned to orally receive vehicle or Cr(D-Phe)(3) (45 μg of elemental chromium/kg/day) for 8-weeks. High-fat-fed mice exhibited impaired whole-body-glucose and -insulin tolerance and elevated serum triglyceride levels compared to normal chow-fed mice. Insulin-stimulated glucose up-take in the gastrocnemius muscles, assessed as 2-[(3)H-deoxyglucose] incorporation was markedly diminished in high-fat fed mice compared to control mice. Treatment with chromium reconciled the high-fat diet-induced alterations in carbohydrate and lipid metabolism. Treatment of cultured, differentiated myotubes with palmitic acid evoked insulin resistance as evidenced by lower levels of insulin-stimulated Akt-phosphorylation, elevated JNK-phosphorylation, (assessed by Western blotting), attenuation of phosphoinositol-3-kinase activity (determined in the insulin-receptor substrate-1-immunoprecipitates by measuring the extent of phosphorylation of phosphatidylinositol by γ-(32)P-ATP), and impairment in cellular glucose up-take, all of which were inhibited by Cr(d-Phe)(3). These results suggest a beneficial effect of chromium-supplementation in insulin resistant conditions. It is likely that these effects of chromium may be mediated by augmenting downstream insulin signaling.
School of Pharmacy, Division of Pharmaceutical Sciences, Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071, USA.
Machender Reddy
MR
Kandadi
M K
MK
Unnikrishnan
Ajaya Kumar Sankara
AK
Warrier
Min
M
Du
Jun
J
Ren
Nair
N
Sreejayan
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D004041:Dietary Fats / Q000009:adverse effects*; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000494:pharmacology*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects
D001786:Blood Glucose; D004041:Dietary Fats; D009942:Organometallic Compounds; C512471:chromium (D-Phenylalanine)3; D010649:Phenylalanine