Exp Mol Med.  2002 Mar;34(1):12-17.

The stimulatory effect of IL-1beta on the insulin secretion of rat pancreatic islet is not related with iNOS pathway

• Jeong IK
• Oh SH
• Chung JH
• Min YK
• Lee MS
• Lee MK
• Kim KW

Abstract

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.

MeSH Terms

Animal
Cells, Cultured
Diabetes Mellitus, Insulin-Dependent/metabolism
Insulin/*secretion
Interleukin-1/*pharmacology
Islets of Langerhans/cytology/*drug effects/metabolism
Male
Nitric Oxide/metabolism
Nitric-Oxide Synthase/genetics/*metabolism
Rats
Rats, Sprague-Dawley
Time Factors
omega-N-Methylarginine/pharmacology