• Clin. Exp. Pharmacol. Physiol. · May 2012

    Long-term in vitro treatment of INS-1 rat pancreatic β-cells by unsaturated free fatty acids protects cells against gluco- and lipotoxicities via activation of GPR40 receptors.

    • Ya Tuo, Dan Dan Feng, Deng-Feng Wang, Jian Sun, Sheng-Bin Li, and Chen Chen.
    • Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
    • Clin. Exp. Pharmacol. Physiol. 2012 May 1;39(5):423-8.

    AbstractG-protein coupled receptor 40 (GPR40) is a membrane-bound G-protein-coupled receptor with high binding affinity to medium- and long-chain free fatty acids (FFAs). Acute activation of GPR40 on pancreatic β-cells causes insulin secretion, whereas prolonged activation may contribute to a deterioration of the effect of saturated FFAs on β-cells. It has been documented that different types of FFAs produce various effects on insulin secretion; however, little information is available regarding the expression of GPR40 and its function after long-term exposure of β-cells to unsaturated FFAs. In the present study, GPR40 expression and function were assessed in INS-1 β-cells after 48 h exposure to different types of unsaturated FFAs. The mRNA and protein expression of GPR40 was increased significantly by long-term exposure of cells to polyunsaturated α-linolenic acid, but not to either oleic acid or linoleic acid. Immunocytochemistry revealed a reduction in the number of insulin-containing granules in cells treated with α-linolenic acid, which was correlated with an increase in cellular expression of GPR40. Basal and glucose-stimulated insulin secretion were markedly suppressed by 48 h treatment of cells with saturated palmitic acid, but not unsaturated α-linolenic acid. By testing various FFAs, it was found that FFA-induced suppression of basal and glucose-stimulated insulin secretion was attenuated by an increase in the degree of unsaturation of the FFAs and GPR40 expression in response to FFA treatment in INS-1 cells. The results of the present study indicate that long-term in vitro treatment of INS-1 rat pancreatic β-cells by unsaturated FFAs protects the cells against from gluco- and lipotoxicities and that this coincides with an increase in GPR40 expression.© 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.

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