Functional and morphological effects of interleukin-1 beta on the perfused rat pancreas.
We recently reported a potentiating effect of recombinant human interleukin-1 beta on glucose-stimulated insulin release from the isolated perfused pancreas. With the aim of determining whether the stimulatory effect of recombinant interleukin-1 beta on the B cell in the intact gland was modulated by varying the concentration, time of exposure to recombinant interleukin-1 beta or B-cell activity, and to elucidate a possible mechanism of action, we measured in the perfused rat pancreas the release of insulin, glucagon and/or prostaglandin E2 according to the following three different protocols: (1) perfusion with 20 ng/ml of recombinant interleukin-1 beta for 92 min at 5 and 20 mmol/l D-glucose (2) perfusion with varying concentrations of recombinant interleukin-1 beta ranging from 0.1 x 10(-3) ng/ml to 100 ng/ml at 5 and 20 mmol/l D-glucose (3) perfusion with 20 ng/ml of recombinant interleukin-1 beta at 5, 11 or 20 mmol/l D-glucose. Furthermore, in a separate set of experiments we examined the influence of the cytokine on the morphology of the endocrine pancreas. Interleukin-1 beta stimulated insulin secretion at 11 and 20 mmol/l D-glucose and potentiated first as well as second phase insulin release in a dose-dependent fashion, with decreasing effect at higher concentrations. Glucagon secretion was also stimulated by recombinant interleukin-1 beta, irrespective of increasing glucose (5, 11, 20 mmol/l) and insulin concentrations. The potentiating effect of recombinant interleukin-1 beta on insulin secretion was evident even after discontinued perfusion with the cytokine, suggesting a priming effect on B-cell function.(ABSTRACT TRUNCATED AT 250 WORDS)
Wogensen
L D
LD
Steno Memorial Hospital, Hagedorn Research Laboratory, Gentofte, Denmark.
Kolb-Bachofen
V
V
Christensen
P
P
Dinarello
C A
CA
Mandrup-Poulsen
T
T
Martin
S
S
Nerup
J
J
D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D008854:Microscopy, Electron; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology
D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D005934:Glucagon; D005947:Glucose; D015232:Dinoprostone