
The cytokine interleukin-1 beta may have an important role in the autoimmune mediated damage of pancreatic Beta cells in insulin-dependent diabetes mellitus. In the present study we have investigated the effects of an interleukin-1 receptor antagonist protein, a blocker of the type I interleukin-1 receptor, on the suppressive actions of recombinant interleukin-1 beta on insulin-producing cells. Brief exposure (1-2 h) of rat and mouse pancreatic islets to 10 ng/ml recombinant interleukin-1 beta induced an 70-80% inhibition of insulin response to glucose after 12 h. These effects were completely counteracted by co-incubation with 100 ng/ml interleukin-1 receptor antagonist protein. When rat islets were cultured for 48 h in the presence of recombinant interleukin-1 beta (5 ng/ml) higher concentrations of interleukin-1 receptor antagonist protein (5000 ng/ml) were required to protect Beta-cell function. Interleukin-1 receptor antagonist protein also counteracted the inhibitory effects of recombinant interleukin-1 beta on the growth of the rat insulinoma cell line RINm5F. These data suggest that interleukin-1 receptor antagonist protein can protect insulin-producing cells from the deleterious effects of recombinant interleukin-1 beta, and that these cells possess type I interleukin-1 receptors.
Male, Time Factors, Pancreatic Neoplasms -- ultrastructure, Cultured -- pathology, Inbred Strains, Receptors, Immunologic -- drug effects, Pancreatic Neoplasms -- pathology, Insulinoma -- ultrastructure, Recombinant Proteins -- pharmacology, Islets of Langerhans -- cytology, Mice, Insulinoma -- pathology, Receptors, Insulin, Tumor Cells, Cultured -- drug effects, Tumor Cells, Cultured -- pathology, Receptors, Immunologic, Cells, Cultured, Cultured, Proteins -- pharmacology, Insulinoma -- metabolism, Sciences bio-médicales et agricoles, Recombinant Proteins, Tumor Cells, Receptors, Immunologic -- physiology, Insulin -- metabolism, Cells, Glucose -- physiology, Sialoglycoproteins, Islets of Langerhans -- ultrastructure, Islets of Langerhans -- metabolism, Islets of Langerhans, Cultured -- ultrastructure, Animals, Interleukin-1 -- pharmacology, Pancreatic Neoplasms -- metabolism, Animal, Immunologic -- physiology, Cultured -- drug effects, Proteins, Receptors, Interleukin-1, Rats, Inbred Strains, Rats, Pancreatic Neoplasms, Disease Models, Animal, Interleukin 1 Receptor Antagonist Protein, Glucose, Disease Models, Tumor Cells, Cultured -- ultrastructure, Insulinoma, Immunologic -- drug effects, Interleukin-1
Male, Time Factors, Pancreatic Neoplasms -- ultrastructure, Cultured -- pathology, Inbred Strains, Receptors, Immunologic -- drug effects, Pancreatic Neoplasms -- pathology, Insulinoma -- ultrastructure, Recombinant Proteins -- pharmacology, Islets of Langerhans -- cytology, Mice, Insulinoma -- pathology, Receptors, Insulin, Tumor Cells, Cultured -- drug effects, Tumor Cells, Cultured -- pathology, Receptors, Immunologic, Cells, Cultured, Cultured, Proteins -- pharmacology, Insulinoma -- metabolism, Sciences bio-médicales et agricoles, Recombinant Proteins, Tumor Cells, Receptors, Immunologic -- physiology, Insulin -- metabolism, Cells, Glucose -- physiology, Sialoglycoproteins, Islets of Langerhans -- ultrastructure, Islets of Langerhans -- metabolism, Islets of Langerhans, Cultured -- ultrastructure, Animals, Interleukin-1 -- pharmacology, Pancreatic Neoplasms -- metabolism, Animal, Immunologic -- physiology, Cultured -- drug effects, Proteins, Receptors, Interleukin-1, Rats, Inbred Strains, Rats, Pancreatic Neoplasms, Disease Models, Animal, Interleukin 1 Receptor Antagonist Protein, Glucose, Disease Models, Tumor Cells, Cultured -- ultrastructure, Insulinoma, Immunologic -- drug effects, Interleukin-1
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