A newly synthetic chromium complex – chromium(phenylalanine)₃ improves insulin responsiveness and reduces whole body glucose tolerance

Abstract

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 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 lg/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.

Cardiac contractile dysfunction in Lep/Lep obesity is accompanied by NADPH oxidase activation, oxidative modification of sarco(endo)plasmic reticulum Ca2+-ATPase and myosin heavy chain isozyme switch

“…A glucose tolerance test was conducted in mice fasted for 12 h by intraperitoneal injection of glucose (2 g/kg body weight). Glucose levels were determined immediately before challenge and 15, 30, 60 and 120 min thereafter [21].…”

Chromium (d‐Phenylalanine)3 Improves Obesity‐Induced Cardiac Contractile Defect in ob/ob Mice

“…The pH of the aqueous solution of the complex is 4.7, and the presence of chloride demonstrates the presence of HCl in the lattice. Based on the stoichiometry, elemental analysis, and spectral studies, the product obtained is a complex containing a 1:3 ratio of chromium to phenylalanine (13).…”

“…Clinical trials have indicated that supplementation with chromium chloride or low-molecular weight complexes of chromium can lower blood glucose levels in the diabetic patient (12). Recent evidence suggests that low-molecular weight organic chromium complexes possess better bioavailability compared with chromium salts (2% to 5% vs. 0.5% to 2%), leading to the development of low-molecular weight organic complexes of chromium as therapeutic agents to counter the diminished insulin effect (13). Chromium picolinate [Cr(pic) 3 ], 1 the most popularly used dietary supplement, has been shown to modulate glucose metabolism and improve dyslipidemia associated with insulin resistance in several animal and human studies (14,15).…”

“…The prooxidant nature of Cr(pic) 3 has greatly limited its therapeutic application and prompted us to seek safer synthetic chromium complexes with a natural amino acid ligand (16). Our laboratory has recently synthesized a lowmolecular weight complex, chromium (D-phenylalanine) 3 [Cr(D-phe) 3 ], which enhances insulin signaling and glucose uptake in adipocytes and improves glucose clearance in an ob/ob obese model of insulin resistance with lesser cytotoxicity compared with Cr(pic) 3 (13,17). Nonetheless, the effect of Cr(D-phe) 3 on heart function under obesity and insulin resistance has not been elucidated.…”

Evaluation of insulin binding and signaling activity of newly synthesized chromium(III) complexes in vitro

“…Though these results were not confirmed in other experiments, they suggest that the mechanisms of Cr action are of high complexity. Additionally, yang et al (49) reported that chromium phenylalanine increased the phosphorylation of (308) tyrosine in Akt inside insulin-stimulated adipocytes in a dose-and time-dependent manner. on the other hand, these authors did not find any influence of the Cr complex on the phosphorylation of the insulin receptor subunit (IRβ).…”