Short-term exposure of rat pancreatic islets to human interleukin-1 beta increases cellular uptake of calcium.
Interleukin-1 (IL-1) may be one of the effector molecules involved in the destruction of the pancreatic islet B cells resulting in insulin-dependent diabetes mellitus. Isolated islets exposed to IL-1 show an acutely increased substrate metabolism and insulin release, which is followed by a metabolic and functional suppression. Since an increased cellular uptake of calcium in the islets may be associated with both nutrient-induced insulin release and cell damage, the effects of recombinant IL-1 beta (rIL-beta) on net cellular calcium uptake by isolated rat pancreatic islets were investigated. In short-term experiments the islets were exposed to 25 U/ml rIL-1 beta for 120 min in the presence of 1.7 mM or 16.7 mM glucose, or 16.7 mM glucose plus 5 mM verapamil. In these experiments rIL-1 beta induced an increase both in net cellular uptake of calcium and in insulin release only in the presence of 16.7 mM glucose. The stimulatory effect of rIL-1 beta at 16.7 mM glucose was blocked by verapamil. By long-term experiments, under tissue culture conditions in the presence of 11.1 mM glucose, islet net calcium uptake, insulin release and glucose oxidation were measured at different time points over a 24-h period. During the first 2 h of incubation 25 U/ml rIL-1 beta effected a significant increase of net calcium uptake, insulin release and glucose oxidation. However, after 4-5 h of incubation with the cytokine no such stimulatory effects were seen. After longer incubations with rIL-1 beta all the islet functions studied were suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)
Borg
L A
LA
Department of Medical Cell Biology, University of Uppsala, Sweden.
Eizirik
D L
DL
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004347:Drug Interactions; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012636:Secretory Rate / Q000187:drug effects; D013268:Stimulation, Chemical; D014700:Verapamil / Q000494:pharmacology
D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D014700:Verapamil; D005947:Glucose; D002118:Calcium