Abstract
It has recently been indicated that tumor necrosis factor-α (TNF-α) production is increased under chronic hyperglycemia and TNF-α has harmful effects on insulin sensitivity and possibly on chronic diabetic complications. Therefore it will be favorable for diabetes treatment if anti-diabetic agents also have anti-TNF-α activities. In this study, we have investigated effects of hypoglycemic sulfonylureas (gliclazide and glibenclamide) and a thiazolidinedione (troglitazone) on lipopolysaccharide-induced TNF-α production, which was evaluated by immunoassay and bioassay, in vivo using mice and partly in vitro using human peripheral blood mononuclear cells. Gliclazide significantly inhibited TNF-α production in vivo and also in vitro at a concentration of 10 −3 mol/l. However, glibenclamide had neither effect on TNF-α production nor action. On the other hand, troglitazone inhibited action rather than production of TNF-α in vivo. In vitro troglitazone (10 −4 mol/l) significantly reduced cytolytic activity of TNF-α against LM cells. These results indicate that gliclazide and troglitazone have inhibitory effect on TNF-α.
Published Version
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