A newly synthetic chromium complex--chromium(phenylalanine)3 improves insulin responsiveness and reduces whole body glucose tolerance.
Low-molecular-weight organic chromium complexes such as chromium picolinate are often used as dietary supplements to improve insulin sensitivity and to correct dyslipidemia. However, toxicity associated with such chromium compounds has compromised their therapeutic value. The aim of this study was to evaluate the impact of a newly synthesized complex of chromium with phenylalanine, Cr(pa)3 on insulin-signaling and glucose tolerance. Cr(pa)3 was synthesized by chelating chromium(III) with D-phenylalanine ligand in aqueous solution. In mouse 3T3-adipocytes, Cr(pa)3 augmented insulin-stimulated glucose-uptake as assessed by a radioactive-glucose uptake assay. At the molecular level, Cr(pa)3 enhanced insulin-stimulated phosphorylation of Akt in a time- and concentration-dependent manner without altering the phosphorylation of insulin receptor. Oral treatment with Cr(pa)3 (150 microg/kg/d, for six weeks) in ob/ob+/+ obese mice significantly alleviated glucose tolerance compared with untreated obese mice. Unlike chromium picolinate, Cr(pa)3 does not cleave DNA under physiological reducing conditions. Collectively, these data suggest that Cr(pa)3 may represent a novel, less-toxic chromium supplement with potential therapeutic value to improve insulin sensitivity and glycemic control in type II diabetes.
Yang
Xiaoping
X
Division of Pharmaceutical Sciences, School of Pharmacy, University of Wyoming, Laramie, WY 82071, USA.
Palanichamy
Kamalakannan
K
Ontko
Allyn C
AC
Rao
M N A
MN
Fang
Cindy X
CX
Ren
Jun
J
Sreejayan
Nair
N
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D005951:Glucose Tolerance Test; D017665:Hydroxyl Radical / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin / Q000378:metabolism
D002843:Chromatin; D007328:Insulin; D011518:Proto-Oncogene Proteins; D019000:Phosphotyrosine; D017665:Hydroxyl Radical; D010649:Phenylalanine; D004247:DNA; D011972:Receptor, Insulin; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose