Inhibitory effects of interleukin 1 on insulin secretion, insulin biosynthesis, and oxidative metabolism of isolated rat pancreatic islets

Endocrinology. 1987 Oct;121(4):1424-31. doi: 10.1210/endo-121-4-1424.


Recent observations suggest a role for interleukin 1 (IL-1), a macrophage-derived cytokine, in the autoimmune B cell destruction, which is observed in type 1 diabetes. In the present study we have investigated the effects of IL-1 and two other cytokines, namely tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) on the pancreatic B cell paying particular attention to insulin production and glucose metabolism. Rat pancreatic islets were isolated and kept in tissue culture for 5 days. The islets were subsequently transferred to media containing medium RPMI 1640 plus 0.5% human serum with or without additions of human recombinant preparations of either IL-1 (25 U/ml), TNF (1000 U/ml), or IFN-gamma (500 U/ml), and cultured for another 48 h. After the culture period the islets were subjected to light microscope examination and different functional tests in short-term incubations in the absence of cytokines. IL-1 was found to reduce insulin release in culture and totally inhibit glucose-stimulated insulin release in short-term incubations. Islet (pro)insulin biosynthesis, glucose oxidation, and oxygen uptake at 16.7 mM glucose were partially inhibited by IL-1. The DNA content of islets cultured with IL-1 was decreased and may partly explain these latter findings. However, inhibition of glucose oxidation could not be seen in islets exposed to IL-1 in short-term experiments only. By light microscopy there were marked signs of degeneration in IL-1 treated islets. TNF and IFN-gamma were essentially without effect on islet morphology or function. The results of this study indicate that IL-1 may be cytotoxic to islet B cells. The primary toxic action of IL-1 seems to involve factors other than an impaired islet glucose metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glucose / metabolism
  • Glucose / pharmacology
  • In Vitro Techniques
  • Insulin / biosynthesis
  • Insulin / metabolism*
  • Insulin Antagonists / pharmacology*
  • Insulin Secretion
  • Interleukin-1 / pharmacology*
  • Islets of Langerhans / metabolism*
  • Male
  • Oxidation-Reduction
  • Oxygen Consumption
  • Rats
  • Rats, Inbred Strains


  • Insulin
  • Insulin Antagonists
  • Interleukin-1
  • Glucose