Association of TNF-α Gene Expression and Release in Response to Anti-Diabetic Drugs from Human Adipocytes in vitro

摘要

Introduction: TNF-α, a proinflammatory cytokine secreted by activated immune cells, and overexpression of it in adipocytes, has an important role in insulin resistance progression and diabetes development. Aim and Objective: Subcutaneous adipocytes derived from mesenchymal stem cells were used for in vitro analysis to find the role of antidiabetic drugs on TNF-α in high glucose-fed adipocytes. Methods: In vitro adipocytes were used along with variable concentration of anti-diabetic drugs. The level of TNF-α was measured by ELISA and the mRNA level was quantified using SYBR-Green real-time PCR. All data were statistically analyzed. Results: The level of TNF-α and the mRNA expression were observed and analyzed with normal adipocytes. TNF-α level and expression of it showed agonistic behavior, ie no change at low concentration while enhances with the increase of glucose. The level was decreased significantly when the adipocytes were treated with metformin ( p =0.015) and pioglitazone ( p =0.020). A combination of drugs showed that the expression of TNF-α was almost the same as for metformin alone. However, insulin increases the TNF-α expression as for pioglitazone. Discussion: Such a report on adipocytes may be helpful for clinical benefits to understand the additional mechanism of adipocytes on the release and expression of TNF-α. However, anti-diabetic drugs including insulin up-regulate the TNF-α gene expression in mild or severe glucose load.