Nitric oxide vs insulin secretion, action and clearance

Excerpt

To the Editor: In their Diabetologia article, Natali and colleagues [1] reported a decrease in glucose tolerance in response to acute inhibition of NO generation by N ^G-nitro-l-arginine methylester (L-NAME), which resulted from a 40% drop in beta cell glucose sensitivity and doubled insulin clearance, whereas peripheral insulin sensitivity did not change. Admittedly, whether conclusions from an acute experiment can apply to a long-term impairment of NO bioavailability remains disputable. Moreover, mice with genetic disruption of endothelial NO synthase, used as a model of chronic NO deficiency, exhibit insulin resistance (IR) in the liver and peripheral tissues [2]. Nevertheless, it can be speculated that depressed insulin secretion and enhanced insulin degradation, when superimposed on concomitant IR, might further impair glucose tolerance and accelerate the development of type 2 diabetes mellitus under conditions associated with reduced NO bioavailability. …