CYTOKINE-INDUCED INHIBITION OF LIPID-SYNTHESIS AND HORMONE-SECRETION BY ISOLATED HUMAN ISLETS

Interleukin-1, tumor necrosis factor, and interleukin-6 inhibit insuli n release and may be cytotoxic to isolated pancreatic islets. These cy tokines have been postulated to play an important role in the beta cel l destruction characteristic of type 1 diabetes. The present study was designed to investigate the effect of the above cytokines on insulin, glucagon, somatostatin, and thyrotropin-releasing hormone secretion b y isolated human islets. In addition, we have investigated if cytokine -induced modifications in hormone secretion are accompanied by modific ations in the ab initio synthesis of any specific lipidic fraction. Al l three cytokines studied, although not modifying insulin and somatost atin release to glucose 5 mmol/L, inhibited the response of both hormo nes to glucose 20 mmol/L. On the other hand, the cytokines almost comp letely blocked islet basal glucagon release, without affecting thyrotr opin-releasing hormone secretion. The added cytokines also suppressed 20 mmol/L [U-C-14]glucose incorporation into both phospholipids and di acylglycerol. Our results demonstrate a beta-, alpha-, and delta-cell, sensitivity to cytokine action. Additionally, they suggest that ab in itio lipid synthesis might be implicated in the mechanism of insulin r elease in human islets.