The effects of oral antidiabetics on adipogenesis related gene expressions in 3T3-L1, AML12 cell lines and their co-cultures

Abstract

The objective of the study was investigated for the effects of oral antidiabetic drugs, how they effect the cells proliferation activities and how they change the expressions of FTO, CD68, NIBAN, and RAN genes which could change insulin signalization and also be effective in the adipogenetic process on 3T3-L1 adipocytes, AML12 hepatocytes and adipocyte-hepatocyte co-cultures. Cell proliferation was examined real time with iCELLigence system and measured for 96 hours each 15 min period. The time and amount of active substances of the oral anti-diabetic drugs which were applied to cells were determined real time according to IC50 value. FTO, CD68 NIBAN and RAN gene expression profiles were determined with qPCR. When single and multiple doses of glipizide and acarbose in co-culture’s were compared respectively, the 24 hour IC50 values were determined as 180 μM and 17 mg/ml in adipocytes; 72 μM and 23 mg/ml in hepatocytes, 41.5 μM and 5 mg/ml in coculture cells. The application of metformin for 24 hour IC50 value in single culture was determined as 175 mM in adipocytes and 2.3 mM in hepatocytes. In the Metformin administered cells. FTO, CD68 and NIBAN gene expressions were decreased in all groups. In the acarbose applied cells FTO and CD68 gene expressions were decreased in all groups. In the acarbose applied cells while NIBAN gene expression was decreased in adipocytes, it was fund to increase in co-cultured adipocytes. In the acarbose applied cells RAN gene expression was found to increase in all groups. Decreasing effects of antidiabetics on CD68 and FTO expressions may show protective effect of drug on inflammation and obesity. In conclusion, oral antidiabetic drug use may be effective in development glucose homeostasis via changing the gene expression of RAN in hepatocytes and adipocytes, this pathway may have therapeutic effect and provide novel strategies for treatment of insulin resistance. 

Keywords

• 3T3-L1 adipocyte,AML12 hepatocyte,iCELLigence system,oral antidiabetics,non-alcholic fatty liver disease,gene expression

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