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

Authors :
Wogensen, L.
Reimers, J.
Nerup, J.
Kolb -Bachofen, V.
Kröncke, K.
Almdal, T.
Mandrup -Poulsen, T.
Source :
Diabetologia; Apr1992, Vol. 35 Issue 4, p331-339, 9p
Publication Year :
1992

Abstract

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 μg of recombinant human interleukin-1 β 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 μg/kg of interleukin-1 daily for 3 or 5 days; (b) the cumulative effects of repetitive intraperitoneal injections of 4 μg/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 μg/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 μg/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. Blood glucose levels significantly increased time-dependently 4-10 h after the third and fifth injection of interleukin-1, and diabetic values (blood glucose >11.0 mmol/l) were observed 6 and 10 h after the fifth injection of interleukin-1. Ten hours after the fifth injection of interleukin-1, diabetic blood glucose levels were observed together with a 50% reduction in plasma insulin concentration. Ultrastructural examination showed no signs of Betacell lysis. In conclusion, interleukin-1 has bimodal effects on glucose homeostasis in vivo, a slight lowering of the blood glucose followed by impaired glucose tolerance and later by diabetic blood glucose levels. Two hours after the last of five daily injections of interleukin-1 impaired glucose tolerance is primarily caused by a state of insulin resistance, whereas diabetic blood glucose levels are associated with inhibition of insulin secretion. Thus, interleukin-1 causes a diabetic state in normal animals, but it remains to be demonstrated that administration of interleukin-1 to normal animals leads to permanent diabetes due to Beta-cell destruction. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0012186X
Volume :
35
Issue :
4
Database :
Complementary Index
Journal :
Diabetologia
Publication Type :
Academic Journal
Accession number :
70809146
Full Text :
https://doi.org/10.1007/BF00401200