Effects Of Elevated Levers Of Palmitic Acid, Rosiglitazone And Fenofibrate On The Expression Of Free Fatty Acid Receptor 1 MRNA In Pancreatic β-Cells

[OBJECTIVE]To study the effects of palmitic acid, rosiglitazone and fenofibrate on the expression of free fatty acid receptor 1/ G protein-coupled receptor 40 (FFAR1/ GPR40) and the function of insulin secretion from in vitro cultured NIT-1 cells.[METHODS]NIT-1 cells were divided into four groups, normal group (NC group), palmitic acid group (PA group), palmitic acid plus rosiglitazone group (RG group) and palmitic acid plus fenofibrate group (FF group). They were cultured respectively for 24 h in vitro. The levers of insulin secretion were measured with radioimmunoassay, intracellular triglyceride contents were determined by a method based on the colorimetric determination of glycerol produced by hydrolysis of neutral lipids and FFAR1/GPR40 mRNA levels were detected by RT-PCR.[RESULTS](1) Impaired glucose-stimulated insulin secretion (GSIS) and increased intracellular triglyceride content were observed in PA group vs NC group. In RG group or FF group, GSIS was improved and intracellular triglyceride content was decreased compared with PA group.(2) Upregulated expression of FFAR1/GPR40 mRNA was found in PA group compared with NC group, and in FF group, not in RG group, the upregulation of FFAR1/GPR40 mRNA expression by palmitic acid was inhibited.[CONCLUSION](1) It is one of the mechanisms of lipotoxicity that high concentration of palmitic acid upregulate the expression of FFAR1/GPR40 mRNA.(2) Rosiglitazone can protect the function of beta cells, but the mechanisms have nothing to do with the regulation of FFAR1/GPR40 mRNA expression.(3) Fenofibrate can ameliorate lipotoxicity via inhibiting the upregulation of FFAR1/GPR40 mRNA expression induced by palmitic acid.