Addition of L-glutamine to a linoleic acid perifusate prevents the fatty acid-induced desensitization of pancreatic islet response to glucose

Previous studies showed that exposure of pancreatic islets to polyunsaturated fatty acids (PUFA) can render the beta cells unresponsive to glucose, thus suggesting the possibility that prolonged obligatory use of lipid preparations containing high concentrations of essential fatty acids during total parenteral nutrition may adversely affect glucose tolerance. In the present study we examined the effect of pretreatment of isolated murine islets with 10 mmol/L linoleate (18:2, ω6) alone or in the presence of 20 mmol/L-glutamine on the response of both alpha and beta cells to 27.7 mmol/L glucose perifusion at 37° C. The incremental areas under the curve/20 mins (AUC/20 mins) for insulin output stimulated by 27.7 mmol/L glucose were 1552.8 ± 276.3 pg and 220.4 ± 163.9 pg (P < 0.001), (n = 6), respectively, before and after treatment with linoleic acid alone. In experiments in which the islets were treated with linoleate in the presence of L-glutamine there was no difference in the incremental insulin AUC/20 mins, in response to 27.7 mmol/L glucose before and after the fatty acid treatment (2051.8 ± 420.5 pg versus 2159.2 ± 317.6 pg, respectively, n = 6). Glucose-induced suppression of glucagon secretion, which was lost after perifusion of islets with the fatty acid alone, was observed when glutamine was added to the linoleate perifusate. In conclusion, the addition of L-glutamine to linoleic acid perifusion of isolated islets completely blocked the PUFA-induced desensitization of both pancreatic alpha and beta cells to glucose effect. © 1993.

Duke Scholars

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