Interleukin 4 impairs rat pancreatic islet function in vitro by an action different to that of interleukin 1.
Cytokines, in particular interleukin 1 beta (IL-1 beta), have been implicated in pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. In the rat prolonged exposure in vitro of islets of IL-1 beta 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-1 beta 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-1 beta 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-1 beta-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-1 beta stimulation of medium nitrite was partly reduced by IL-4. Compared to the action exerted by IL-1 beta the inhibitory action of IL-4 on rat islet function was moderate, and the latter action seems to be independent on nitric oxide production.
Sandler
S
S
Department of Medical Cell Biology, Uppsala University, Sweden.
Sternesjö
J
J
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000009:adverse effects*; D015847:Interleukin-4 / Q000009:adverse effects*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D007375:Interleukin-1; D009573:Nitrites; D015847:Interleukin-4; D004247:DNA; D005947:Glucose