Abstract

BACKGROUND
The inhibitory effect of IL-1 on the insulin secretion has been validated in pathogenesis of type 1 diabetes, but complex results about the stimulatory effect of IL-1 have been reported. The aims of this study are to clarify the effects of IL-1 on insulin secretion of pancreatic islets and to investigate the mechanisms in terms of preproinsulin synthesis, inducible NOS expression, and calcium channel activity. METHODS: Islets were isolated from male Sprague-Dawley (SD) rat by modified Lacy-Kostianovsky's method. After islets were treated with different concentrations (0, 0.5, 5, 50, 500 pmol/L) and exposure time (2, 6, 24 hours) of IL-1 , morphology, viability, static stimulation of insulin to glucose, insulin content, preproinsulin mRNA expression, iNOS mRNA expression and calcium channel activity were measured. RESULTS: 1) Viability of islets was reduced in high concentrations of long term exposure of IL-1 . 2) Insulin secretion was stimulated in islets treated with 5, 50, and 500 pmol/L of IL-1 for 2 hours and 0.5 pmol/L for 6 hours. It was inhibited in 5, 50, and 500 pmol/L for 6 and 24 hours. 3) Insulin content was not significantly different regardless of concentration and exposure time of IL-1 . 4) Preproinsulin mRNA expression increased in islets treated with 50, 500 pmol/L of IL-1 for 2 hours. After 24 hours, it decreased in dose dependent manner. 5) iNOS mRNA expression was detectable after 2 hours in the presence of IL-1 , peaks at 6 hour and decreased after 24hours. It was increased above 5 pmol/L of IL-1 in dose dependent manner. 6) Activities of the voltage-dependent Ca2+ channels were not different among groups. CONCLUSION: IL-1 plays a positive role in terms of insulin secretion and insulin synthesis in high concentration of short term or low concentration of long term. These effects of IL-1 might be neither dependent of iNOS pathway nor Ca2+ channel activity.

• Keywords: IL-1;Islet;Insulin;Preproinsulin synthesis;Inducible NOS;Ca2+ channel