Intra-peritoneal administration of interleukin-1 beta induces impaired insulin release from the perfused rat pancreas.
Previous studies have demonstrated a stimulatory effect of interleukin-1 beta (IL-1 beta) on insulin and glucagon release from the perfused rat pancreas, accompanied by selective lysis of 20% of beta-cells as assessed by electronmicroscopy. However, we have not observed an inhibitory action of IL-1 beta on insulin release from the perfused pancreas as shown for isolated islets. To test whether periodical exposure of the endocrine pancreas to circulating IL-1 beta in vivo affects insulin release from the intact perfused pancreas, rats were treated with daily intraperitoneal injections of 4 micrograms IL-1 beta/kg or saline for 5 days. On day 5 the pancreata were isolated 2 h after the last injection and perfused from 0 to 72 min with 11 mmol/l D-glucose and from 72 to 84 min with 20 mmol/l D-glucose. Saline or IL-1 beta was added from 12 to 72 min. In pancreata from animals pre-treated with IL-1 beta glucose-stimulated as well as IL-1 beta potentiated glucose-stimulated insulin release was almost completely abolished. Furthermore, a decline in insulin release was observed at 11 mmol/l D-glucose, in contrast to an increase in insulin release in controls. The total extractable insulin content in pancreata from IL-1 beta pre-treated rats was higher than in pancreata from saline-treated controls. In contrast to the inhibitory effect of in vivo administration of IL-1 beta on beta-cell function glucagon secretion was stimulated. These observations suggest that circulating IL-1 beta is an important modulator of alpha- and beta-cell secretory function in vivo and that IL-1 beta should be considered a contributory pathogenetic factor in the development of insulin-dependent (type 1) diabetes mellitus.
Wogensen
L
L
Steno Memorial Hospital/Hagedorn Research Laboratory, Gentofte, Denmark.
Helqvist
S
S
Pociot
F
F
Johannesen
J
J
Reimers
J
J
Mandrup-Poulsen
T
T
Nerup
J
J
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011921:Rats, Inbred WKY; D011994:Recombinant Proteins / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D005934:Glucagon; D005947:Glucose