http://worldcat.org/entity/work/id/135722820

The impairing effect of a prolonged free fatty acid elevation on glucose stimulated insulin secretion

Reduced glucose-stimulated insulin secretion (GSIS) characterizes both type 1 and type 2 diabetes mellitus. An elevation in plasma free fatty acids (FFA) is characteristic of both obesity and absolute or relative insulin deficiency. Previous work by our laboratory has demonstrated that prolonged elevation of plasma FFA impairs GSIS. We hypothesized that preexisting islet inflammation/oxidative stress modulates the FFA effect on GSIS (Study#1) and that this is mediated by FFA-induced oxidative stress (Study#2). Our results indicate that the FFA-induced defect in GSIS is accentuated in pre-diabetic BB rats (model of type 1 diabetes) with insulitis (Study# 1), suggesting that islet inflammation modulates the effect of FFA. We also found that some antioxidants prevent the impairing effect of a prolonged FFA elevation on GSIS, suggesting that oxidative stress plays a role in mediating this effect (Study#2). Thus, antioxidants/anti-inflammatory agents may have therapeutic potential in type 2 diabetes and in slow-onset type 1 diabetes.

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