Endocrinology, Vol 122, 2393-2398, Copyright © 1988 by Endocrine Society

ARTICLES

Interleukin-1 inhibits glucose-modulated insulin and glucagon secretion in rat islet monolayer cultures

A Rabinovitch, C Pukel and H Baquerizo
Department of Medicine, University of Miami School of Medicine, Florida 33101.

Recent observations suggest a role for interleukin-1 (IL-1), a polypeptide product of macrophage/monocytic cells, in the immune- mediated destruction of pancreatic islet beta-cells observed in type 1 diabetes. In this study, we investigated the effects of IL-1 on both alpha- and beta-cell secretory functions in rat islet cell monolayer cultures. Insulin release was 97% inhibited after 6 h of incubation in RPMI-1640 medium (11 mM glucose) containing 1 U/ml IL-1 and 96% inhibited after 24 h of incubation in medium containing 0.1 U/ml IL-1. The cell content of insulin in the monolayers was decreased by 66% (P less than 0.01) after 4 days of incubation in 10 U/ml IL-1; however, after a further 8-day incubation in IL-1-free medium, cell insulin content recovered fully. In contrast, cell glucagon content was decreased by 77% (P less than 0.001) after 4 days of incubation in 10 U/ml IL-1 and did not recover after a further 8-day incubation in IL-1- free medium. After an 18-h preincubation in medium with 0.1 and 1 U/ml IL-1, insulin release responses to 16.7 mM glucose were abolished in 4- h incubations, whereas responses to 0.1 mM 3-isobutyl-1-methylxanthine were normal, and after a further 2 and 5 days of incubation in IL-1- free medium, insulin responses to 16.7 mM glucose recovered fully. Similarly, the inhibitory effect of 16.7 mM glucose on glucagon release was lost after an 18-h preincubation in 0.1 and 1 U/ml IL-1, and did not recover fully after 2 and 5 days in IL-1-free medium, whereas the stimulatory effect of 3-isobutyl-1-methylxanthine on glucagon release was not affected by IL-1. We conclude that 1) IL-1 inhibits glucose- dependent and not cAMP-dependent mechanisms of insulin and glucagon release; 2) inhibition of glucose-stimulated insulin release by IL-1 is reversible, whereas the effect on glucose-modulated glucagon release is not; and 3) IL-1 causes a reversible decrease in the insulin content of islet cells and an irreversible decrease in glucagon content. These actions of IL-1 do not appear to account for the beta-cell-specific destruction of islets characteristic of type 1 diabetes.

This article has been cited by other articles:

				X. F. Mao, X. S. Piao, C. H. Lai, D. F. Li, J. J. Xing, and B. L. Shi Effects of {beta}-glucan obtained from the Chinese herb Astragalus membranaceus and lipopolysaccharide challenge on performance, immunological, adrenal, and somatotropic responses of weanling pigs J Anim Sci, December 1, 2005; 83(12): 2775 - 2782. [Abstract] [Full Text] [PDF]

				A. Hoorens, G. Stangé, D. Pavlovic, and D. Pipeleers Distinction Between Interleukin-1-Induced Necrosis and Apoptosis of Islet Cells Diabetes, March 1, 2001; 50(3): 551 - 557. [Abstract] [Full Text]