Pioglitazone Ameliorates Atorvastatin-Induced Islet Cell Dysfunction through Activation of FFA1 in INS-1 Cells

Figure 3

Effect of atorvastatin, pioglitazone, and FFA1-PLC signaling pathway inhibitors on basal insulin secretion and potassium-stimulated insulin secretion in INS-1 cells. (a) Administration of 10 μM pioglitazone for 24 h preserved the increased basal insulin secretion by 20 μM atorvastatin. (b) Administration of 10 μM pioglitazone for 24 h prevented the reduction in potassium-stimulated insulin secretion induced by 20 μM atorvastatin. (c) FFA1 antagonist 2 μM GW1100 significantly reduced the potassium-stimulated insulin secretion after 24 h of incubation. (d) Knockdown of FFA1 using siRNA significantly reduced the potassium-stimulated insulin secretion. Atorvastatin and FFA1 siRNA together also decreased the potassium-stimulated insulin secretion. (e) The preventive effect of pioglitazone on the atorvastatin-induced impairment of insulin secretion was abolished by knockdown of FFA1 using siRNA or the PLC inhibitor U-73122 in INS-1 cells. (f) qRT-PCR assay analysis of insulin expression in INS-1 cells treated with atorvastatin, pioglitazone, FFA1 siRNA, and U-73122 for 24 h. β-Actin was detected as control. Negative control siRNA (NC-siRNA) was used for cell transfection as negative control to rule out any nonspecific effects that the siRNA transfection might have on insulin. Values presented are the deviations of three independent experiments. and compared to control. compared to 20 μM atorvastatin treatment alone. and compared to atorvastatin and pioglitazone treatment together.

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