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

Year 2019, Volume: 2 Issue: 1, 29 - 37, 20.07.2019

Meliha Koldemir Gündüz , Mehtap Çevik Penbe Çağatay Belgin Süsleyici

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

Supporting Institution

Marmara University Scientific Research Projects Commission

Project Number

FEN-C-DRP-131113-0433

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