title: 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.
abstract: G-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.
authors.affiliation: Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Tuo
authors.forename: Dan Dan
authors.initials: DD
authors.lastname: Feng
authors.forename: Deng-Feng
authors.initials: DF
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Sheng-Bin
authors.initials: SB
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage*; D005947:Glucose / Q000633:toxicity*; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism* / Q000502:physiology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; C473035:G-protein-coupled receptor 40, rat; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D005947:Glucose