Development and Analysis of Novel Therapeutic Targets to Improve Pancreatic β-Cell Function in Type 2 Diabetes.

Development and Analysis of Novel Therapeutic Targets to Improve Pancreatic β-Cell Function in Type 2 Diabetes. Yakugaku Zasshi. 2016;136(12):1623-1629 Authors: Kaneko YK Abstract  Pancreatic β-cell dysfunction is a major feature of type 2 diabetes. Therefore maintenance of β-cell function is essential to preventing the onset and progression of type 2 diabetes. To elucidate the mechanisms underlying the regulation of insulin secretion and β-cell survival, we particularly focused on the roles of gasotransmitters in pancreatic β-cells. Nitric oxide (NO) and hydrogen sulfide (H2S) are recognized as toxic gases. However, they are also vital physiological and pathophysiological mediators in various cell types. NO, generated from L-arginine by reactions catalyzed by NO synthases, is a well-known neurotransmitter and smooth muscle relaxation factor. In pancreatic β-cells, induction of nitric oxide synthase 2 (NOS2) by inflammatory cytokines generates a large amount of NO, which contributes to the impairment of β-cell function and induction of β-cell apoptosis, which are, in turn, involved in the development of type 1 diabetes. In contrast, a physiological level of NO, generated by constitutive NOS (cNOS), acts as a positive or negative regulator of insulin secretion and β-cell survival, depending on concentration. H2S generated from L-cysteine has been shown to play a role of neuromodulator, and this gas possesses cytoprotective ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research