Functional characteristics of rat pancreatic islets maintained in culture after exposure to human interleukin 1.
Recent observations suggest a role for interleukin 1 beta (IL-1) in the autoimmune beta-cell destruction observed in type I (insulin-dependent) diabetes mellitus. We investigated the acute and long-term effects of IL-1 on pancreatic beta-cell function in vitro. Rat pancreatic islets were isolated and kept in tissue culture for 5 days. The islets were subsequently transferred to media containing RPMI-1640 plus 1% human serum with or without human recombinant IL-1 beta (300 pM) and cultured for another 48 h. The islets were examined either immediately after IL-1 exposure (day 0) or after an additional 6-day culture period without IL-1. On day 0, IL-1 was found to totally inhibit glucose-stimulated insulin release, partially inhibit glucose oxidation, and induce a decrease in islet DNA content. However, these islets were able to release insulin after stimulation with glucose plus theophylline, although the absolute rate of insulin secretion was lower than that of the control group. After 6 days in culture, the insulin-secretory response to glucose and the glucose oxidation rates of the IL-1-pretreated islets were completely restored, but there remained a reduced islet DNA content. We conclude that IL-1 is cytotoxic to islet beta-cells. However, surviving beta-cells are able to recover their functional capacity after a period of inhibited function.
Eizirik
D L
DL
Department of Medical Cell Biology, Uppsala University, Sweden.
Strandell
E
E
Bendtzen
K
K
Sandler
S
S
D000818:Animals; D046508:Culture Techniques; D004247:DNA / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D013806:Theophylline / Q000494:pharmacology
D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D004247:DNA; D013806:Theophylline; D005947:Glucose