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Inhibition of tumor necrosis factor-alpha with anti-diabetic agents
1Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
Abstract:
It has recently been indicated that tumor necrosis factor-alpha (TNF-alpha) production is increased under chronic hyperglycemia and TNF-alpha 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-alpha activities. In this study, we have investigated effects of hypoglycemic sulfonylureas (gliclazide and glibenclamide) and a thiazolidinedione (troglitazone) on lipopolysaccharide-induced TNF-alpha 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-alpha production in vivo and also in vitro at a concentration of 10(-3) mol/l. However, glibenclamide had neither effect on TNF-alpha production nor action. On the other hand, troglitazone inhibited action rather than production of TNF-alpha in vivo. In vitro troglitazone (10(-4) mol/l) significantly reduced cytolytic activity of TNF-alpha against LM cells. These results indicate that gliclazide and troglitazone have inhibitory effect on TNF-alpha.
Insights
Gliclazide and troglitazone, diabetes medications, were found to inhibit tumor necrosis factor-alpha (TNF-alpha). This suggests potential benefits for diabetes treatment by targeting inflammation alongside blood sugar control.
Area of Science:
- Immunology
- Endocrinology
- Pharmacology
Background:
- Increased tumor necrosis factor-alpha (TNF-alpha) production is linked to chronic hyperglycemia.
- TNF-alpha negatively impacts insulin sensitivity and may contribute to diabetic complications.
Purpose of the Study:
- To investigate the anti-TNF-alpha activities of gliclazide, glibenclamide, and troglitazone.
- To determine if these anti-diabetic agents can modulate TNF-alpha production or action.
Main Methods:
- Lipopolysaccharide (LPS)-induced TNF-alpha production was measured in vivo (mice) and in vitro (human peripheral blood mononuclear cells).
- Immunoassay and bioassay techniques were employed to quantify TNF-alpha.
- The effects of gliclazide, glibenclamide, and troglitazone on TNF-alpha production and activity were assessed.
Main Results:
- Gliclazide significantly inhibited TNF-alpha production both in vivo and in vitro.
- Glibenclamide showed no effect on TNF-alpha production or action.
- Troglitazone inhibited TNF-alpha action in vivo and reduced its cytolytic activity in vitro.
Conclusions:
- Gliclazide demonstrates inhibitory effects on TNF-alpha production.
- Troglitazone exhibits inhibitory effects on TNF-alpha action.
- These findings suggest that gliclazide and troglitazone may offer dual benefits in diabetes management by addressing both hyperglycemia and inflammation.