The Protecting Effect Of Pioglitazone On The Abnormal Expression Of βTC-3 Cell GPR40 Induced By Free Fatty Acids

BackgroundDyslipidiaemia plays an important role in the pathogenesy of diabete mellitus. Long-term exposure to high concentrations of free fatty acids will impact the function of pancreaticβ-cell and lead to diabete mellitus.G protein coupled receptor 40(GPR40) is specific recepter for long line fatty acids.By bonding to GPR40, FFA can increase the intracellular Ca2+ concentration and stimulate the secretion of insulin。Peroxisome proliferators activated receptorγ(PPAR-γ)is a kind of transcription factors. Pioglitazone is a high selective agonist of PPAR-γ, By acting on nuclear receptor of peripheral tissue, it can reduce insulin resistance. Also it can directly regulate the function of pancreaticβcell by acting on PPAR-γon pancreaticβcell and improve the ability of insulin secretion.ObjectiveThe effects of abnormal free fatty acids and the protection action of pioglitazone on gene expression of GPR40 inβTC-3 cell were investigated.MethodsExperimental study based onβTC-3 cell.(1)βTC-3 cell was subject to different treatments with a blank and three concentrations of FFA, that is 0.25mmol/L, 0.5mmol/L and 1.0mmol/L for 12 hours and 24 hours respectively. Semi-quantitative RT-PCR analysis was used to determined the RNA expression level of GPR40.(2)βTC-3 cell was preincubated with 0.1μmol/L,1μmol/L,10μmol/L pioglitazone for 6 hours , and then 1 mmol/L FFA was added and the cells were incubated for another 24 hours. The RNA expression level of GPR40 was assayed by Semi-quantitative RT-PCR.ResultsAfter the cells were incubated with different concentration of FFA for 12 hours , there was no statistically significant difference among each groups. At 24 hours,no statistical difference existed between the 0.25 mmol/L FFA group and the control group either. But compared to the control group,the RNA content of GPR40 inβTC-3 cell was significantly decreased after incubated with both 0.5 and 1mmol/L free fatty acids for 24 hours( P <0.05).Compared to the 0.25 mmol/L FFA group,the RNA content of GPR40 inβTC-3 cell was also significantly decreased after incubated with both 0.5 and 1 mmol/L free fatty acids (P<0.05). There was no statistical difference between the 0.5mmol/L FFA and 1 mmol/L FFA group.Though no statistically significant difference was found between 0.1μmol/L pioglitazone and 1.0mmol/L FFA co-treated group and the 1.0mmol/L FFA group, both 1and 10μmol/L pioglitazone and 1.0mmol/L FFA co-treated group could increase the RNA content of GPR40 inβTC-3 cell compared to 1mmol/L FFA group ( P <0.01).ConclusionsFree fatty acids may inhibit the gene expression of GPR40 ,while pioglitazone can protect the expression ofβTC-3 cell GPR40 from FFA-induced impairment.