Interleukin 4 impairs rat pancreatic islet function in vitro by an action different to that of interleukin 1

Cytokines, in particular interleukin 1β (IL-1β), have been implicated in pancreatic β-cell destruction in insulin-dependent diabetes mellitus. In the rat prolonged exposure in vitro of islets of IL-1β leads to nitric oxide formation, impaired glucose metabolism and inhibition of insulin secretion. I...

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Bibliographic Details
Published in:Cytokine (Philadelphia, Pa.) Pa.), 1995-04, Vol.7 (3), p.296-300
Main Authors: Sandler, Stellan, Sternesjö, Johnny
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
DNA - metabolism
Glucose - metabolism
Glucose - pharmacology
Insulin - metabolism
Insulin Secretion
interleukin 1
interleukin 4
Interleukin-1 - adverse effects
Interleukin-4 - adverse effects
Islets of Langerhans - drug effects
Islets of Langerhans - physiology
Male
Nitric oxide
Nitrites - metabolism
Oxidation-Reduction
pancreatic islets
Protein Biosynthesis
Rats
Rats, Sprague-Dawley
β-cells
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Summary:Cytokines, in particular interleukin 1β (IL-1β), have been implicated in pancreatic β-cell destruction in insulin-dependent diabetes mellitus. In the rat prolonged exposure in vitro of islets of IL-1β leads to nitric oxide formation, impaired glucose metabolism and inhibition of insulin secretion. Interleukin 4 (IL-4) has been shown to be able to modulate nitric oxide formation in other cell systems. In the present study we have investigated the effect of IL-4 alone and in combination with IL-1β on islet cells. For this purpose isolated rat pancreatic islets were cultured for 42 h in medium supplemented with 0, 0.1, 1.0 or 10 ng/ml of human IL-4 in the absence or presence of 25 U/ml of IL-1β during the last 24 h of culture. IL-4 alone dose-dependently decreased the islet glucose oxidation rate and the glucose-stimulated insulin release. Furthermore, the cytokine potentiated IL-1β-induced reduction in the islet DNA content and (pro)insulin biosynthesis rate. The medium nitrite accumulation, as an index of nitric oxide formation, was not influenced by IL-4 (10 ng/ml) alone, whilst IL-1β stimulation of medium nitrite was partly reduced by IL-4. Compared to the action exerted by IL-1β the inhibitory action of IL-4 on rat islet function was moderate, and the latter action seems to be independent on nitric oxide production.
ISSN:1043-4666
1096-0023
DOI:10.1006/cyto.1995.0036