Not all insulin secretagogues sensitize pancreatic islets to recombinant human interleukin 1 beta.
The purpose of this study was to test the influence of different insulin secretagogues on interleukin 1 beta mediated injury to isolated rat pancreatic islets. Islets were exposed to interleukin 1 beta for 6 days. During exposure, beta-cells were stimulated with glucose (11 mmol/l vs 3.3 mmol/l) or with non-nutrients as tolbutamide (250 mumols/l), iso-butyl 1-methyl-xanthine (50 mumols/l), or glucagon (10 mg/l). At 3.3 mmol/l of glucose, 60,000 U/l of interleukin 1 beta caused an inhibition of medium insulin accumulation to 62 +/- 5% of control from 48 h to 6 days of exposure, whereas islet DNA content was unaffected. At 11 mmol/l of glucose, interleukin 1 beta dose-dependently decreased medium insulin accumulation (e.g. 60,000 U/l of interleukin 1 beta, 12 +/- 3% of control) and islet content of DNA (60,000 U/l of interleukin 1 beta, 60 +/- 8% of control). During beta-cell stimulation with tolbutamide, interleukin 1 beta caused inhibition of insulin accumulation to 36 +/- 9% of control. In contrast, on islets stimulated with iso-butyl 1-methyl-xanthine or glucagon, the effects of interleukin 1 beta were equivalent to those on non-stimulated islets. These differences were paralleled by differences in the interleukin 1 beta effect on islet morphology. In conclusion, high beta-cell activity (as measured by islet insulin release) may increase islet susceptibility to interleukin 1 beta, however, depending upon the intracellular pathway through which insulin secretion is activated.
Steno Memorial Hospital, Gentofte, Denmark.
J
J
Johannesen
S
S
Helqvist
J
J
Nerup
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D004247:DNA / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
D003470:Culture Media; D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D004247:DNA; D005934:Glucagon; D014044:Tolbutamide; D005947:Glucose; D015056:1-Methyl-3-isobutylxanthine