STRAIN-DEPENDENT DIFFERENCES IN SENSITIVITY OF RAT BETA-CELLS TO INTERLEUKIN-1-BETA IN-VITRO AND IN-VIVO - ASSOCIATION WITH ISLET NITRIC-OXIDE SYNTHESIS

The aim of this study was to investigate whether strain-dependent diff erences in beta-cell sensitivity to interleukin (IL) 1 beta exist in v itro and in vivo and if so, whether these differences correlate to var iations in IL-1 beta-induced islet inducible nitric oxide synthase (iN OS) mRNA expression and nitrite production in vitro and islet iNOS pro tein content in vivo. Isolated islets of Langerhans in vitro hom Wista r-Kyoto/Mollegarden (WK/Mol) rats were sensitive to the inhibitory eff ect of IL-1 beta on accumulated and acute insulin secretion, whereas i slets from Brown Norway/Charles River (BN/CR) rats were resistant, Fur thermore, IL-1 beta induced higher islet iNOS mRNA expression and nitr ic oxide production from WK/Mol islets compared with BN/CR islets, WK/ Mol, WK/CR, BN/Mol, BN/CR, and Lewis-Scripps/Mol (LS/Mol) rats receive d one daily injection of recombinant human IL-1 beta (4.0 mu g/kg) or vehicle for 5 days, AU the strains investigated were susceptible to IL -1 beta-induced changes in body weight, food intake, temperature, and plasma glucagon and corticosterone. However, IL-1 beta induced hypergl ycemia and impairment of beta-cell glucose responsiveness in WK/Mol an d LS/Mol rats, but not in BN rats, Furthermore, IL-1 beta-induced isle t iNOS expression in vive determined by immunostaining was greater in WK/Mol rats compared with WK/CR and BN/CR rats, No restriction fragmen t length polymorphisms, using 20 restriction enzymes, were identified in the iNOS gene in six rat strains including BioBreeding rats, In con clusion, the relative resistance of BN rat islets to IL-1 beta-induced inhibition of beta-cell function in vitro was associated with lower i slet iNOS mRNA expression and nitrite production in this strain, Furth er, the resistance of BN rats to IL-1 beta-induced hyperglycemia was a ssociated with a lower islet iNOS expression in vivo.