Strain-Dependent Differences in Sensitivity of Rat β-Cells to Interleukin 1β In Vitro and In Vivo

The aim of this study was to investigate whether straindependent differences in β-cell sensitivity to interleukin (IL) 1β exist in vitro and in vivo and if so, whether these differences correlate to variations in IL-1β-induced islet inducible nitric oxide synthase (iNOS) mRNA expression and nitrite production in vitro and islet iNOS protein content in vivo. Isolated islets of Langerhans in vitro from Wistar-Kyoto/Møllegården (WK/Mol) rats were sensitive to the inhibitory effect of IL-1β on accumulated and acute insulin secretion, whereas islets from Brown Norway/Charles River (BN/CR) rats were resistant. Furthermore, IL-1β induced higher islet iNOS mRNA expression and nitric 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 received one daily injection of recombinant human IL-1β (4.0 μg/kg) or vehicle for 5 days. All the strains investigated were susceptible to IL-1β–induced changes in body weight, food intake, temperature, and plasma glucagon and corticosterone. However, IL-1β induced hyperglycemia and impairment of β-cell glucose responsiveness in WK/Mol and LS/Mol rats, but not in BN rats. Furthermore, IL-1β–induced islet iNOS expression in vivo determined by immunostaining was greater in WK/Mol rats compared with WK/CR and BN/CR rats. No restriction fragment length polymorphisms, using 20 restriction enzymes, were identified in the iNOS gene in six rat strains including BioBreeding rats. In conclusion, the relative resistance of BN rat islets to IL-1β–induced inhibition of β-cell function in vitro was associated with lower islet iNOS mRNA expression and nitrite production in this strain. Further, the resistance of BN rats to IL-1β–induced hyperglycemia was associated with a lower islet iNOS expression in vivo.