The role of G protein-coupled receptor 40 in lipoapoptosis in mouse beta-cell line NIT-1.
Free fatty acids (FFAs) exert divergent effects on beta-cells. Acute exposure to FFAs stimulates insulin secretion, whereas chronic exposure impairs beta-cell function and induces apoptosis. The G protein-coupled receptor 40 (GPR40) is preferentially expressed in beta-cells and is activated by a wide range of FFAs. In this study, we used small interfering RNA technology and apoptosis assay in mouse beta-cell NIT-1 to address the role of GPR40 in beta-cell lipoapoptosis and function. Results showed that palmitate induced beta-cell apoptosis, which was not mediated through GPR40, whereas oleate protected NIT-1 cells from palmitate-induced lipoapoptosis, which was mediated at least in part through GPR40. Moreover, by detecting the activation of the phosphatidylinositol 3-kinase and MAP kinase (MAPK) pathways, we found that oleate promoted the activation of extracellular signal-regulated protein kinase-MAPK pathway mainly via GPR40, increased the expression of early growth response gene-1, leading to the anti-lipoapoptotic effect on NIT-1 cells. It was suggested that GPR40 might be implicated in the control of beta-cell mass plasticity and GPR40 probably provide a link between obesity and type 2 diabetes.
Zhang
Ying
Y
Department of Endocrinology, The Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Xu
Mingtong
M
Zhang
Shaoling
S
Yan
Li
L
Yang
Chuan
C
Lu
Wensheng
W
Li
Yan
Y
Cheng
Hua
H
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D005230:Fatty Acids, Nonesterified / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D005230:Fatty Acids, Nonesterified; C473036:Ffar1 protein, mouse; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled