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 interleukin-1 (IL-1) on insulin and glucagon secretion. To understand the mechanism of these effects, we performed localization and characterization of IL-1 receptors (IL-1R) in pancreas using a quantitative autoradiography method and recombinant human (rh) [125I]IL-1 alpha as a ligand. Frozen sections of pancreas were studied in control (C3H/He) and nonobese diabetic (NOD) mice (a model of autoimmune type I diabetes). Compared to splenic IL-1R, a very high density of specific IL-1R (> 4-fold that in spleen) was found on the islets of Langerhans in both strains. In C3H/He mice, competition experiments demonstrated the presence of one high affinity binding site (Ki = 3.4 and 3.2 x 10(-10) M; binding capacity, 137 and 122 fmol/mg protein for rhIL-1 alpha and rhIL-1 beta, respectively), comparable to type I IL-1R described on T-lymphocytes. In prediabetic NOD mice, these IL-1R were expressed with the same density, affinity, and specificity as in the control strain. Before the onset of diabetes, the expression of IL-1R protein on the islet cells appears to be entirely normal. In contrast, in diabetic NOD mice, IL-1R are sharply decreased, correlating with the intensity of islet destruction. In conclusion, the localization and high density of IL-1R on the mouse islets of Langerhans complement previous studies showing the presence of messenger RNA for type I IL-1R on the islets of Langerhans. These results support a direct physiological effect of IL-1 on pancreatic hormones, such as insulin and glucagon, and a potential role of IL-1R in the pathogenesis of type I diabetes.
Unité de la Rage, Institut Pasteur, Paris, France.
M
M
Jafarian-Tehrani
A
A
Amrani
F
F
Homo-Delarche
C
C
Marquette
M
M
Dardenne
F
F
Haour
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D016688:Mice, Inbred NOD; D017472:Receptors, Interleukin-1 / Q000032:analysis*; D013154:Spleen / Q000378:metabolism
D007375:Interleukin-1; D017472:Receptors, Interleukin-1