Subarna Karmaker

Amelioration of Hyperglycemia and Metabolic Syndromes in Type 2 Diabetic KKAy Mice by Poly(γ-glutamic acid)oxovanadium(IV) Complex

Recently, we found that poly(γ‐glutamic acid)oxovanadium(IV) complex (VO(γ‐pga)) exhibits a potent antidiabetic activity in streptozotocin (STZ)‐induced type 1 diabetic mice. This result prompted us to examine its ability to treat the type 2 diabetic model KKAy mice with insulin resistance. We studied the in vivo antidiabetic activity of VO(γ‐pga), compared with that of vanadium(IV) oxide sulfate (VS) as control. Both compounds were orally administered at doses of 5–10 mg (0.1–0.2 mmol) V kg−1 body mass to the KKAy mice for 30 days. VO(γ‐pga) normalized the hyperglycemia within 21 days, whereas VS lowered the blood glucose concentration only by a small degree. In addition, the glucose intolerance, HbA1c level, hyperinsulinemia, hypercholesterolemia, and hyperleptinemia were significantly improved in VO(γ‐pga)‐treated KKAy mice compared with those treated with VS. Based on these observations, VO(γ‐pga) is proposed to be the first orally active oxovanadium(IV)‐polymer complex for the efficacious treatment of not only type 2 diabetes but also metabolic syndrome in animals.

Studies on the mechanism of the reaction of tetrakis({1-me-thylpyridinium-4-yl}porphyrinato)iron(III) pentaperchlorate with hydrogen peroxide

The reaction of the 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrinatoiron(III) cation, [FeIII(TMPyP)]5+ (1; prepared as the pentaperchlorate), with hydrogen peroxide (H2O2) in aqueous solution was studied by spectrophotometric methods. The porphyrin 1 was rapidly oxidized with an excess of H2O2 under aerobic conditions to the oxo-iron(IV) porphyrin, [FeIVO(TMPyP)]4+ (2), having UV-visible absorption maxima at 436 and 450 nm. Computer deconvolution of the time-resolved absorption spectra revealed that the absorption spectra < 0.5 s were not reproduced well by a simple combination of the two spectra of 1 and 2, indicating that transient species were formed at the initial stage. Addition of sodium nitrite (NaNO2), which is thought to be a one-electron donor, to the stoichiometric reaction mixture of 1 and H2O2 increased the initial formation rate of 2. The presence of uric acid (UA) caused a significant delay in the formation of 2. The delay of the appearance of 2 was directly proportional to the starting concentration, [UA]0, but other kinetic profiles were not changed significantly. Based on these observations and the kinetic analysis, we confirmed the involvement of the oxo-iron(IV) porphyrin radical cation, [FeIVO(TMPyP•)]5+ (3), as a compulsory intermediate in the rate-determining step of the overall reaction, 1 + H2O2→ 2, with a rate constant k = 4.4 × 104 M−1.s−1. The rate constants for the reaction between 2 and NaNO2, and between 2 and UA were estimated to be 9.0 M−1s−1 and 5.45 × 106M−1.s−1, respectively.