ROLE OF RECEPTOR-BINDING AND GENE-TRANSCRIPTION FOR BOTH THE STIMULATORY AND INHIBITORY EFFECTS OF INTERLEUKIN-1 IN PANCREATIC BETA-CELLS

被引：25

作者：

EIZIRIK, DL

TRACEY, DE

BENDTZEN, K

SANDLER, S

机构：

[1] Department of Medical Cell Biology, Uppsala University, Uppsala

[2] Hypersensitivity Diseases Research, The Upjohn Company, Kalamazoo, MI

[3] Laboratory of Medical Immunology, Medical Department TTA, University Hospital, Copenhagen

来源：

AUTOIMMUNITY | 1992年 / 12卷 / 02期

关键词：

INTERLEUKIN-1; RECEPTOR; PANCREATIC ISLETS; INSULIN RELEASE; (PRO)INSULIN BIOSYNTHESIS;

D O I：

10.3109/08916939209150319

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

A brief exposure of pancreatic islets to the cytokine interleukin-1β (IL-lβ induces an initial stimulatory phase, which is followed by inhibition of islet function and eventually βcell damage. In the present study we have investigated the effects of IRAP, a blocker of type I IL-1 receptor and actinomycin D, an inhibitor of DNA transcription, on both the stimulatory and inhibitory effects of IL-β on rat pancreatic islets in vitro. The two test agents counteracted the initial stimulatory actions of IL-1β on both islet glucose-induced insulin release and glucose oxidation rates. Furthermore, cycloheximide, an inhibitor of protein synthesis, could also prevent the early IL-l/?-induced stimulation of insulin release. When islets were exposed for 1 hr to IL-1β and studied after 12 hr, there was a 75% inhibition of glucose induced insulin release, a 50% decrease in glucose oxidation rates and a 30% decrease in (pro)insulin biosynthesis. These effects were completely counteracted by coincubation with IRAP or actinomycin D, but were not affected by coincubation with pertussis toxin. Islet exposure to IL-Ia also induced a 60-80% inhibition of glucose-induced insulin release after 12 hr. As observed with rIL-1β IRAP was also able to block the suppressive effects of IL-1 a on islet function. Mouse islets exposed for 2 hr to IL-1β and studied after 12 hr presented a 50% decrease in the glucose-induced insulin release. This effect was completely blocked by coincubation with a rat monoclonal antibody generated against the type I mouse IL-1 receptor. These data suggest that most or all effects of IL-lβ on rat pancreatic islets are dependent on binding to surface IL-1 receptors and activation of gene transcription. It remains to be clarified which are the second messengers generated following IL-1β binding to its receptor and which are the gene(s) transcribed following pancreatic islet exposure to the cytokine. © 1992 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

引用

页码：127 / 133

页数：7

共 46 条

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