Receptor-specific regulation of ERK1/2 activation by members of the “free fatty acid receptor” family

Seljeset, Sandra; Siehler, Sandra

doi:10.3109/10799893.2012.692118

Cited by 59 publications

(41 citation statements)

References 20 publications

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“…This study confirmed the relationship between linoleic acid treatment and activation of the ERK-MAP kinase pathway (Fig. 2), consistent with a previous report [21]. The microarray data showed that treatment with linoleic acid resulted in upregulation of transforming growth factor, beta receptor II (Tgfbr2), calcium channel, voltage-dependent, gamma subunit 5 (Cacng5), calcium channel, voltage-dependent, beta 4 subunit (Cacnb4), and protein kinase C, beta (PrkcB), and downregulation of ribosomal protein s6 kinase, 90 kDa, polypeptide 6 (Rps6ka6) and interleukin 1, alpha (Il1α).…”

Section: Discussionsupporting

confidence: 93%

“…Since the involvement of extracellular signal-regulated kinase 1/2 (ERK1/2) in the GPR40-mediated signaling pathway was suggested [6,20], a recent report demonstrated that FFA-mediated ERK1/2 activation was through c-RAF (RAF, a proto-oncogene serine/threonine-protein kinase) and MEK1/2 (ERK kinase) via Rac1 [21]. Although attention was focused on changes in intracellular Ca 2+ , the possible involvement of ERK1/2 in GPR40-mediated insulin secretion remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Differential Gene Expression in GPR40-Overexpressing Pancreatic β-cells Treated with Linoleic Acid

Kim

Han

Jung

et al. 2015

Korean J Physiol Pharmacol

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"G protein-coupled receptor 40" (GPR40), a receptor for long-chain fatty acids, mediates the stimulation of glucose-induced insulin secretion. We examined the profiles of differential gene expression in GPR40-activated cells treated with linoleic acid, and finally predicted the integral pathways of the cellular mechanism of GPR40-mediated insulinotropic effects. After constructing a GPR40-overexpressing stable cell line (RIN-40) from the rat pancreatic β-cell line RIN-5f, we determined the gene expression profiles of RIN-5f and RIN-40. In total, 1004 genes, the expression of which was altered at least twofold, were selected in RIN-5f versus RIN-40. Moreover, the differential genetic profiles were investigated in RIN-40 cells treated with 30 µM linoleic acid, which resulted in selection of 93 genes in RIN-40 versus RIN-40 treated with linoleic acid. Based on the Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG, http://www.genome.jp/kegg/), sets of genes induced differentially by treatment with linoleic acid in RIN-40 cells were found to be related to mitogen-activated protein (MAP) kinase- and neuroactive ligand-receptor interaction pathways. A gene ontology (GO) study revealed that more than 30% of the genes were associated with signal transduction and cell proliferation. Thus, this study elucidated a gene expression pattern relevant to the signal pathways that are regulated by GPR40 activation during the acute period. Together, these findings increase our mechanistic understanding of endogenous molecules associated with GPR40 function, and provide information useful for identification of a target for the management of type 2 diabetes mellitus.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Differential Gene Expression in GPR40-Overexpressing Pancreatic β-cells Treated with Linoleic Acid

Kim

Han

Jung

et al. 2015

Korean J Physiol Pharmacol

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“…Moreover, activation of FFAR1 decreased OA-induced lipid accumulation in HepG2 cells through a p38-dependent pathway. The MAPK pathway is involved in the biological functions of FFAR1 (Seljeset & Siehler 2012). FFAR1 activates ERK-MAPK pathway to control the plasticity of the b-cell mass and improve glycemic control (Zhang et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Activation of free fatty acid receptor 1 improves hepatic steatosis through a p38-dependent pathway

Ou¹,

Lu³

et al. 2014

Journal of Molecular Endocrinology

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Hepatic steatosis is highly correlated with insulin resistance and diabetes. Although, it has been demonstrated that activation of free fatty acid receptor 1 (FFAR1) by agonists showed benefits for the improvement of diabetes, the effects of FFAR1 agonists on hepatic steatosis were unknown. In this study, a high fat diet (HFD)-induced hepatic steatosis animal model was utilized to evaluate the effects of an FFAR1 agonist, GW9508, on hepatic lipid accumulation, and HepG2 hepatoma cells were also used to clarify the possible mechanisms. Administration of GW9508 significantly decreased the hepatic lipid accumulation with decreased expressions of lipogenesis-related proteins in HFD mice. Knockdown of hepatic Ffar1 by lentiviral vectors containing short hairpin RNA targeted to Ffar1 diminished the effect of GW9508 in HFD mice. In addition, GW9508 decreased oleic acid-induced lipid accumulation in HepG2 cells by decreases in the expression of lipogenesis-related proteins. Moreover, GW9508 downregulated the expression of sterol regulatory element-binding protein 1 (SREBP1) through a p38-dependent pathway, whereas knockdown of Ffar1 in HepG2 cells diminished the effect of GW9508 on the decrease in SREBP1. Considering all these results together, GW9508 exerts a therapeutic effect to improve hepatic steatosis through a p38-dependent pathway. Thus, investigation of chemicals that act on FFAR1 might be a new strategy for the treatment of hepatic steatosis. Key Words" free fatty acid receptor 1 " hepatic steatosis " insulin resistance " p38-MAPK " sterol regulatory element-binding protein

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“…FFAR2 couples to G q and G i pathways, whereas FFAR3 is presumed to couple exclusively to the pertussis toxin-sensitive G i pathway (102,103). Both receptors have also been demonstrated to activate MAPK (103,109), which has been associated with GLP1 release from EEC cell lines in response to a number of stimuli (82,110). SCFA-dependent GLP1 secretion was significantly impaired in Ffar2 knockout mice, which also exhibited reduced circulating GLP1 concentrations, supporting a role for FFAR2 signaling in GLP1 secretion (108,111).…”

Section: Gut Microbiota Host Defense and Eec Signalingmentioning

confidence: 99%

Gut chemosensing mechanisms

Psichas¹,

Reimann²,

Gribble³

2015

J. Clin. Invest.

205

176

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Receptor-specific regulation of ERK1/2 activation by members of the “free fatty acid receptor” family

Abstract: The results demonstrate a novel role of Rac in GPCR-mediated ERK1/2 signaling, and that GPCRs belonging to the same family can regulate ERK1/2 activation by different receptor-specific mechanisms.

Cited by 59 publications

References 20 publications

Differential Gene Expression in GPR40-Overexpressing Pancreatic β-cells Treated with Linoleic Acid

Differential Gene Expression in GPR40-Overexpressing Pancreatic β-cells Treated with Linoleic Acid

Activation of free fatty acid receptor 1 improves hepatic steatosis through a p38-dependent pathway

Gut chemosensing mechanisms

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