Differences in long-term effects of l-glutamine and d-glucose on insulin release from rat pancreatic islets

Abstract

We have compared the effects of long-term exposure to l-glutamine or l-glucose on nutrient-induced insulin release from pancreatic islets of the rat. After 3 days of culture islets were finally tested in 1 h incubations for insulin responses to 16.7 mM of glucose, glutamine, leucine or a combination of leucine and glutamine. After culture at 11 mM glucose + 2 mM glutamine (A), glucose, leucine and glutamine stimulated release to a similar extent from islets. After culture at 1.7 mM glucose + 10 mM glutamine (B), only leucine stimulated insulin release. After culture at 11 mM glucose + 10 mM glutamine (C), both leucine and glutamine increased the insulin response. After culture at 1.7 mM glucose and 2 mM glutamine (D), only glutamine slightly stimulated release. After culture in high glutamine (B or C), a combination of leucine and glutamine significantly inhibited release as compared to leucine alone. A switch in culture media from B to A for 1 h prior to final incubations revived insulin release in response to glucose but not to glutamine. The reverse switch (A to B) abolished both subsequent glucose- and glutamine-induced insulin release. A switch from D to B revived an insulin response to leucine. Exposure of B-cells to 11 mM glucose during 30 min in another experimental system (perfused pancreas) induced a significant insulin response to subsequent stimulation with glutamine; this response was, however, only 17% of that to glucose per se observed in the same experiments. Islet 14CO 2 production from [ 14C]glutamine was higher after culture medium A than in B, but the percent increase in 14C production was similar when the concentration of glutamine was changed from 1.7 to 16 mM during oxidation experiments. In contrast, production of 14CO 2 from [ 14C]glucose was similar after culture in A or B in the presence of 1.7 mM glucose, whereas 16.7 mM glucose increased glucose oxidation less after culture in B than in A. We conclude that previous glucose causes a general enhancement of B-cell responsiveness, whereas previous glutamine exerts both stimulatory and inhibitory effects on B-cell function. The latter effect may be linked to interference by glutamine with glucose metabolism of the B-cells.