Interleukin-1 induced impairment in pancreatic islet oxidative metabolism of glucose is potentiated by tumor necrosis factor.
Recent observations suggest that human interleukin-1 (IL-1) causes functional impairment and death of pancreatic B-cells. This action seems to be potentiated by another cytokine, tumor necrosis factor (TNF). In the present investigation, the effects of recombinant human (r)IL-1 (10, 30 and 150 pmol/l), and a combination of rIL-1 and human rTNF (25 micrograms/l), on islet glucose metabolism were examined in the presence of D-[5-3H] and D-[6-14C) glucose. The utilization of glucose was not affected by rIL-1 or rIL-1 plus rTNF. However, rIL-1 induced a 40% decrease in glucose oxidation, which was further potentiated by the addition of rTNF. rTNF alone did not impair islet glucose utilization or oxidation. It is concluded that rIL-1 induces a perturbation of islet glucose handling, mainly at the mitochondrial level. This impairment in the oxidative metabolism of glucose is further increased by the addition of rTNF.
Eizirik
D L
DL
Department of Medical Cell Biology, Uppsala University, Sweden.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose