The stimulatory effect of IL-1beta on the insulin secretion of rat pancreatic islet is not related with iNOS pathway.
Interleukin 1 (IL-1) is a pleiotropic cytokine with the potential to destroy pancreatic beta-cells, and thought to be involved in the pathogenesis of type I diabetes mellitus. Expression of inducible nitric oxide synthase (iNOS) and subsequent NO formation induced by IL-1beta may impair an islet function in rodents. Inhibition of iNOS may protect against cytokine-induced beta-cell suppression, although cytokines might also induce NO-independent impairment. To examine the role of NO in the IL-1beta treated cells, rat islets were treated with various concentrations (0, 0.5, 5, 50, 500 pmol/L) of IL-1beta with or without NG-monomethyl-L-arginine (NMMA; a competitive inhibitor of nitiric oxide synthase) for 2 or 6 h. Insulin secretion was stimulated in islets treated with 5, 50, and 500 pmol/ L of IL-1beta for 2 h and 0.5 pmol/L for 6 h, respectively. The stimulatory effect of IL-1beta on the insulin secretion of rat islets was not prevented by NMMA. Nitrate concentration was increased in a time- and concentration-dependent manner. Nitrate production was inhibited by NMMA. iNOS mRNA expression was increased at concentrations more than 5 pmol/L of IL-1beta in a dose dependent manner. iNOS mRNA was detectable after 2 h and peaked at 6 h but decreased after 24 h. These results suggested that the stimulatory effect of IL-1beta on the insulin secretion of rat islets is independent of iNOS-related NO production of IL-1beta and the enzyme activity of nitric oxide synthase.
Jeong
In-Kyung
IK
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Oh
Seung-Hoon
SH
Chung
Jae-Hoon
JH
Min
Yong-Ki
YK
Lee
Myung-Shik
MS
Lee
Moon-Kyu
MK
Kim
Kwang-Won
KW
D000818:Animals; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D019323:omega-N-Methylarginine / Q000494:pharmacology
D007328:Insulin; D007375:Interleukin-1; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat