Prostaglandins inhibit pancreatic beta-cell replication and long-term insulin secretion by pertussis toxin-insensitive mechanisms but do not mediate the actions of interleukin-1 beta.
The effects of exogenous prostaglandins, inflammatory mediators known to be increased in pancreatic beta-cells by IL-1 beta, on the replication and long-term insulin secretion by beta-cells were investigated. Prostaglandins E1, E2, and F2 alpha suppressed beta-cell proliferation and long-term insulin secretion, thus mimicking the effects of IL-1 beta. The actions of prostaglandins were not prevented by pertussis toxin pretreatment. Additionally, the cyclooxygenase inhibitor indomethacin could not prevent the effects of IL-1 beta. It is concluded that prostaglandins suppress beta-cell growth and long-term insulin secretion without participation of pertussis-toxin sensitive GTP-binding proteins. In addition, although their synthesis is increased by IL-1 beta, prostaglandins seemingly do not convey the inhibitory actions of this cytokine in the beta-cell.
Sjöholm
A
A
Department of Molecular Medicine, Rolf Luft Center for Diabetes Research, Karolinska Institute, Karolinkska Hospital (L6:01B), Stockholm, Sweden. ake@enk.ks.se
D000818:Animals; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000502:physiology*; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism*; D037342:Pertussis Toxin; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007328:Insulin; D007375:Interleukin-1; D011453:Prostaglandins; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins