Repetitive in vivo treatment with human recombinant interleukin-1β modifies Beta-cell function in normal rats

• Published in: Diabetologia Vol. 35; no. 4; pp. 331 - 339
• Main Authors: WOGENSEN, L. D, REIMERS, J, NERUP, J, KOLB-BACHOFEN, V, KRÖNCKE, K.-D, ALMDAL, T, MANDRUP-POULSEN, T
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-04-1992
• Subjects: Animals; Biological and medical sciences; Blood Glucose - metabolism; Body Weight - drug effects; Corticosterone - blood; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Glucagon - blood; Glucagon - metabolism; Insulin - blood; Insulin - metabolism; Insulin Secretion; Interleukin-1 - pharmacology; Islets of Langerhans - drug effects; Islets of Langerhans - physiology; Islets of Langerhans - ultrastructure; Male; Medical sciences; Microscopy, Electron; Organ Size - drug effects; Rats; Rats, Inbred WKY; Recombinant Proteins - pharmacology; Reference Values; Endocrinopathy; Immunopathology; Animal model; Pancreatic hormone; Rat; Rodentia; Cytokine; Autoimmune disease; Exploration; Interleukin 1β; Insulin; Biological activity; Pathology; Vertebrata; Mammalia; B-Cell; Insulin dependent diabetes; Recombinant protein; Endocrine pancreas
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/BF00401200

It is unknown whether interleukin-1 exerts a bimodal effect on Beta-cell function in vivo, and whether interleukin-1 has a diabetogenic action in normal animals. We therefore studied: (a) acute effects 2 h after an intraperitoneal bolus injection of 4 micrograms of recombinant human interleukin-1 beta per kg body weight on blood glucose, plasma levels of insulin, glucagon and corticosterone in Wistar Kyoto rats, either untreated or pre-treated with 4 micrograms/kg of interleukin-1 daily for 3 or 5 days; (b) the cumulative effects of repetitive intraperitoneal injections of 4 micrograms/kg interleukin-1 on blood glucose, glucose tolerance, plasma levels of insulin, glucagon and corticosterone, pancreatic insulin content and pancreatic ultrastructure; and (c) blood glucose and plasma concentrations of insulin, glucagon and corticosterone 10 h after the last of five intraperitoneal injections of interleukin-1, at which time point the inhibitory effect of short-term interleukin-1 exposure on insulin secretion reaches its nadir in vitro. A single injection of 4 micrograms/kg of interleukin-1 caused a slight, but significant lowering of blood glucose 2 h after interleukin-1 injection with no significant changes in plasma insulin and in spite of increases in plasma glucagon and corticosterone. A lowering of blood glucose 2 h after interleukin-1 administration was reproduced with 40, but not 0.4 micrograms/kg of interleukin-1, and was also seen in interleukin-1 pre-treated rats. Two hours after the fifth injection of interleukin-1, intraperitoneal glucose tolerance was impaired with elevated plasma insulin and corticosterone levels and increased pancreatic insulin content, indicating a state of insulin resistance.