THE EFFECT OF ANTI-DIABETIC DRUGS ON THE INFLAMMATORY CYTOKINES IN HUMAN IN VITRO SUBCUTANEOUS ADIPOCYTES.
Madhukar Saxena*, Dinesh Raj Modi, Sanjay Singh and Anand Prakash
Mesenchymal Stem Cells differentiated into subcutaneous adipocytes were used for the study of in vitro effects of antidiabetic drugs including metformin, pioglitazone and insulin on inflammatory cytokines in glucose induced diabetic human adipocytes. Glucose induction in adipocytes mimics the diabetic model in vitro by differentiating mesenchymal stem cells and confirmed by oil red O staining which stains lipid droplets in adipocytes. Adipocytes were incubated in growth media containing variable concentration of glucose (5-20mM) with different anti-diabetic drugs with variable concentrations. Cytokines IL-1Î², IL-6, IL-12, IL-18, TNF-Î±, Leptin, Visfatin and Adiponectin were measured using ELISA. Student t-test (two - tailed) was used for statistical analysis. Variable fluctuations were observed in the present study in relation to cytokine secretions with anti-diabetic drugs. Finally, inflammation of cytokines decreases when metformin and pioglitazone were used in combination in in-vitro study. In conclusion, current data demonstrates that in whole human subcutaneous adipocytes metformin, pioglitazone and combination of both limits the regulation of inflammatory cytokines. However, pioglitazone and metformin in combination as well as insulin up-regulates IL-1Î², IL-6, IL-12, IL-18, TNF-Î±, Leptin, Visfatin and Adiponectin protein secretion in vitro in mild diabetic status and highly up-regulate in severe diabetic status. This effect of anti-diabetic drugs on adipose tissue represents an additional mechanism through which this may induce clinical benefits. Further studies are required to better understand the molecular pathway of this up-regulation in humans.
Keywords: Adipocytes, diabetes, cytokines, metformin, pioglitazone, insulin.
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