Repetitive in vivo treatment with human recombinant interleukin-1 beta modifies beta-cell function in normal rats.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Wogensen
L D
LD
Steno Memorial and Hvidøre Hospital, Gentofte, Denmark.
Reimers
J
J
Nerup
J
J
Kolb-Bachofen
V
V
Kröncke
K D
KD
Almdal
T
T
Mandrup-Poulsen
T
T
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011921:Rats, Inbred WKY; D011994:Recombinant Proteins / Q000494:pharmacology*; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D005934:Glucagon; D003345:Corticosterone