Homologous desensitization of pancreatic beta cells to glucose response by polyunsaturated fatty acids

We have shown recently that a mixture of 10 mM linoleic acid (18:2,ω6) and 5 mM linoleic acid (18:3,ω3) enhanced insulin secretion by microdissected islets. In the present study, our aim was to examine the effect of a prestimulus with this mixture of 10 mM linoleic acid and 5 mM linoleic acid on glucose and arginine-stimulated insulin response, by perifused isolated islets. Insulin secretion by untreated (control) islets estimated as integrated area under the curve (AUC/ 20 mins) above basal during three pulses of 27.7 mM glucose separated by 20 min periods of basal (washout) perifusions were 2950 ± 585 pg, 5185 ± 1258 pg, and 2410 ± 921 pg, a greater response (P < 0.03) being obtained during the second glucose challenge. The insulin response of the islets to the glucose challenge was blunted profoundly if the islets were first exposed to a 20 min period of perifusion with the fatty acid mixture followed by a 20 min washout. Thus, the insulin AUC/20 min decreased from a control value of 2410 ± 921 pg to 337 ± 201 pg (P < 0.03) after prestimulus with the fatty acids. In contrast, fatty acid exposed islets were still responsive to 10 mM arginine. These data suggest that (1) a mixture of 10 mM linoleic acid and 5 mM linolenic acid can desensitize isolated perifused islets to glucose but not arginine; and (2) glucose intolerance associated with lipemia may result, at least in part, from a direct effect on the islets of Langerhans. © 1991.

Duke Scholars

Author Warner Miller Burch Jr. Medicine, Endocrinology, Metabolism, and Nutrition