Inhibitory effects of interleukin 1 on insulin secretion, insulin biosynthesis, and oxidative metabolism of isolated rat pancreatic islets.
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.
Sandler
S
S
Department of Medical Cell Biology, Uppsala University, Sweden.
Andersson
A
A
Hellerström
C
C
D000818:Animals; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism*; D007329:Insulin Antagonists / Q000494:pharmacology*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D007329:Insulin Antagonists; D007375:Interleukin-1; D005947:Glucose