LOCALIZATION AND CHARACTERIZATION OF INTERLEUKIN-1 RECEPTORS IN THE ISLETS OF LANGERHANS FROM CONTROL AND NONOBESE DIABETIC MICE

Numerous in vivo and in vitro studies have shown the effects of interl eukin-1 (IL-1) on insulin and glucagon secretion. To understand the me chanism of these effects, we performed localization and characterizati on of IL-1 receptors (IL-1R) in pancreas using a quantitative autoradi ography method and recombinant human (rh) [I-125]IL-1 alpha as a ligan d. Frozen sections of pancreas were studied in control (C3H/He) and no nobese diabetic (NOD) mice (a model of autoimmune type I diabetes). Co mpared to splenic IL-1R, a very high density of specific IL-1R (>4-fol d that in spleen) was found on the islets of Langerhans in both strain s. In C3H/He mice, competition experiments demonstrated the presence o f one high affinity binding site (K-i = 3.4 and 3.2 x 10(-10) M; bindi ng capacity, 137 and 122 fmol/mg protein for rhIL-1 alpha and rhIL-1 b eta, respectively), comparable to type I IL-1R described on T-lymphocy tes. In prediabetic NOD mice, these IL-1R were expressed with the same density, affinity, and specificity as in the control strain. Before t he onset of diabetes, the expression of IL-1R protein on the islet cel ls appears to be entirely normal. In contrast, in diabetic NOD mice, I L-1R are sharply decreased, correlating with the intensity of islet de struction. In conclusion, the localization and high density of IL-1R o n the mouse islets of Langerhans complement previous studies showing t he presence of messenger RNA for type I IL-1R on the islets of Langerh ans. These results support a direct physiological effect of IL-1 on pa ncreatic hormones, such as insulin and glucagon, and a potential role of IL-1R in the pathogenesis of type I diabetes.