Peroxynitrite has been implicated in β-cell dysfunction and insulin resistance in obesity. Chemical catalysts that destroy peroxynitrite, therefore, may have therapeutic value for treating type 2 diabetes. To this end, we have recently demonstrated that Mn(III) bis(hydroxyphenyl)-dipyrromethene complexes, SR-135 and its analogues, can effectively catalyze the decomposition of peroxynitrite in vitro and in vivo through a 2-electron mechanism (Rausaria et al. 2011). To study the effects of SR-135 on glucose homeostasis in obesity, B6D2F1 mice were fed with a high fat-diet (HFD) for 12 weeks and treated with vehicle, SR-135 (5 mg/kg), or a control drug SRB for 2 weeks. SR-135 significantly reduced fasting blood glucose and insulin levels, and enhanced glucose tolerance as compared to HFD control, vehicle or SRB. SR-135 also enhanced glucose-stimulated insulin secretion based on ex vivo studies. Moreover, SR-135 increased insulin content, restored islet architecture, decreased islet size, and reduced tyrosine nitration and apoptosis. These results suggest that a peroxynitrite decomposing catalyst enhances β-cell function and survival under nutrient overload.

The enzyme Biliverdin Reductase is utilized to aid in the breakdown of heme into bilirubin through the reduction of biliverdin. This is observed in both the yellow pigment in bruising and the jaundice coloring when liver failure occurs due to neurotoxicity. Prior studies have been restricted to rat and Guinea Pig organs. Throughout this experiment we examined enzyme activity of this enzyme in the bovine liver, kidney, spleen and brain then compared activity to that in mammalian species including porcine, bison, and rats. With a standard assay, the enzyme activity throughout the purification process was measured by observing the optimum of product (bilirubin) at 450 nm. The experimentation done on the fresh bovine liver was used as the standard for comparison due to previous experimentation done in this lab in the spring of 2010. Rats biliverdin activity was used to ensure results were comparable to previously designed experiments such as Kutty and Maines (J. Biol. Chem., 256, 3956–3963, 1981). This partial purification and comparative analysis allowed for a further understanding of the Biliverdin Reducatase throughout mammalians and its importance within various organs.