Endocrinology, Vol 128, 1611-1616, Copyright © 1991 by Endocrine Society

ARTICLES

Short exposure of rat pancreatic islets to interleukin-1 beta induces a sustained but reversible impairment in beta-cell function: influence of protease activation, gene transcription, and protein synthesis

DL Eizirik, K Bendtzen and S Sandler
Department of Medical Cell Biology, Uppsala University, Sweden.

In an attempt to gain further knowledge about the mechanism of action of recombinant interleukin-1 beta (rIL-1 beta) on rat pancreatic beta- cells, we studied the effects of short term rIL-1 beta exposure (50 U/ml for 1 h) on islet function over the next 72 h. There was an initial increase in glucose-induced insulin release, followed by a decrease in islet function, reaching a nadir (values of insulin release about 20% of those observed in control islets) 10-12 h after treatment with the cytokine. Thereafter, the islets recovered their function, reaching levels of insulin secretion similar to the control values after 72 h. Short term exposure to rIL-1 beta did not induce a decrease in either islet DNA or islet insulin content. Using this experimental approach, we tested whether 1-h incubation of islets in the presence of various agents plus rIL-1 beta could counteract the inhibitory effects of the cytokine 10-12 h later. Both actinomycin-D (5 micrograms/ml), an inhibitor of DNA transcription, and N alpha-p-tosyl-L-lysine chloromethyl ketone (0.1 mM), a protease inhibitor, could protect the islets. There was also a weak protection by dimethyl urea (61 mM), a free radical scavenger, but no protection by cycloheximide (10 micrograms/ml), an inhibitor of protein synthesis, or amiloride (12.5 microM), a blocker of Na+/H+ exchange. In a subsequent series of experiments, the islets were exposed for 6 h to different test agents after the initial 1-h exposure to rIL-1 beta. In this context, there was a clear protection by cycloheximide and actinomycin-D and a lesser protection by N alpha-p-tosyl-L-lysine chloromethyl ketone. These data suggest that early steps of the actions of rIL-1 beta on rat pancreatic islets are mediated by protease activation and gene transcription, followed by protein synthesis. The identity of the protein(s) remains to be clarified.

This article has been cited by other articles:

				K. L A Souza, E. Gurgul-Convey, M. Elsner, and S. Lenzen Interaction between pro-inflammatory and anti-inflammatory cytokines in insulin-producing cells J. Endocrinol., April 1, 2008; 197(1): 139 - 150. [Abstract] [Full Text] [PDF]

				P. O. T. Tran, C. E. Gleason, and R. P. Robertson Inhibition of Interleukin-1{beta}-Induced COX-2 and EP3 Gene Expression by Sodium Salicylate Enhances Pancreatic Islet {beta}-Cell Function Diabetes, June 1, 2002; 51(6): 1772 - 1778. [Abstract] [Full Text] [PDF]

				P. O. T. Tran, C. E. Gleason, V. Poitout, and R. P. Robertson Prostaglandin E2 Mediates Inhibition of Insulin Secretion by Interleukin-1beta J. Biol. Chem., October 29, 1999; 274(44): 31245 - 31248. [Abstract] [Full Text] [PDF]

				M. Pelegrin, J. C. Devedjian, C. Costa, J. Visa, G. Solanes, A. Pujol, G. Asins, A. Valera, and F. Bosch Evidence from Transgenic Mice That Interferon-beta May Be Involved in the Onset of Diabetes Mellitus J. Biol. Chem., May 15, 1998; 273(20): 12332 - 12340. [Abstract] [Full Text] [PDF]