Metabolism and beta-cell function of rat pancreatic islets exposed to human interleukin-1 beta in the presence of a high glucose concentration.
It has been postulated that one of the factors causing immune-mediated pancreatic beta-cell destruction in insulin-dependent diabetes mellitus (IDDM) is interleukin-1 (IL-1). Rat pancreatic islets exposed to human recombinant IL-1 beta (rIL-1 beta) for 48 h in vitro exhibit a markedly reduced glucose-stimulated insulin secretion. Also, a deleterious effect of glucose on beta-cell function, especially under conditions of a reduced beta-cell mass, which may exist in the early phase of IDDM has been suggested. In this study the response of rat pancreatic islets in vitro to a combination of the cytokine and high glucose concentration have therefore been assessed. Thus, islets were cultured for 48 h at either 11.1 or 56 mM glucose with or without 25 U/ml rIL-1 beta. Exposure to the cytokine reduced the islet DNA content at both glucose concentrations by 20-25%. In short-term incubations in the absence of rIL-1 beta after the preceding culture with the cytokine, the glucose-stimulated insulin release was reduced by 70% in islets cultured at 11.1 mM glucose and by only 40% after culture at 56 mM glucose, when compared to the corresponding control islets. The utilization of D-[5-3H]glucose, i.e., the catabolism of glucose in the glycolytic pathway, was the same in all groups of islets. However, the D-[6-14C]glucose oxidation rate, i.e., the metabolism of glucose in the Krebs cycle, was reduced by about 65% in rIL-1 beta exposed islets kept at 11.1 mM glucose and 46% in islets cultured at 56 mM glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Sandler
S
S
Department of Medical Cell Biology, Uppsala University, Sweden.
Bendtzen
K
K
Eizirik
D L
DL
Strandell
E
E
Welsh
M
M
Welsh
N
N
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003864:Depression, Chemical; D004357:Drug Synergism; D004734:Energy Metabolism / Q000187:drug effects; 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* / Q000378:metabolism; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012636:Secretory Rate / Q000187:drug effects
D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; D005947:Glucose