Free fatty acids induce cholecystokinin secretion through GPR120

Tanaka, Toshiki; Katsuma, Susumu; Adachi, Tomohiko; Koshimizu, Taka-aki; Hirasawa, Akira; Tsujimoto, Gozoh

doi:10.1007/s00210-007-0200-8

Cited by 238 publications

(183 citation statements)

References 17 publications

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“…Furthermore, it is also evident that any effects of orally administered GPR120 agonists on insulin secretion are likely to be mediated mainly by indirect actions on the intestine. This is because GPR120 is expressed on intestinal enteroendocrine cells where it regulates the secretion of incretins such as GIP, GLP-1 and cholecystokinin [130][131][132][133][134]. Therefore, on the basis of these considerations, it seems unlikely that GPR120 plays any direct role in regulating insulin secretion.…”

Section: Gpr120mentioning

confidence: 99%

G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell

Morgan¹,

Dhayal²

2009

Biochemical Pharmacology

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It is increasingly clear that some of the effects of both free and derivatised long chain fatty acids in pancreatic beta-cells are mediated by a group of G-protein coupled receptors. Some of these display close structural homology while others are more divergent. This Commentary reviews the expression and functional roles of three such molecules, GPR40, GPR119 and GPR120. GPR40 is the best characterised of this group and appears to mediate the acute stimulatory effects of long chain fatty acids on insulin secretion. GPR40 has also been proposed as a potential mediator of fatty acid toxicity but this is more controversial. GPR119 is also involved in stimulation of insulin secretion and responds primarily to ethanolamine derivatives of long chain fatty acids and also to some lysophospholipids rather than to free fatty acids. It may represent a useful target for the development of new insulin secretagogues aimed to enhance insulin release in patients with type 2 diabetes. GPR120 is the most enigmatic of the lipid responsive cell-surface receptors and its function remains to be established. It has been proposed to play a cytoprotective role in certain other cell types but it is unclear whether it fulfils a similar function in beta-cells.

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Section: Gpr120mentioning

confidence: 99%

G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell

Morgan¹,

Dhayal²

2009

Biochemical Pharmacology

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“…[3][4][5] It has been proposed to have an important role in regulating lipid and glucose metabolism by stimulating the release of incretin peptide hormones such as cholecystokinin and glucagon-like-peptide-1. 6,7 More recently, GPR120 has been shown to exert effects in regulating inflammation, mediating insulin sensitization and reducing obesity. 8,9 However, there is no report about the expression of GPR120 in tumors, and the role of GPR120 in tumor development is unknown, even though GPR120 is abundantly expressed in intestine.…”

Section: Introductionmentioning

confidence: 99%

Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis and migration in human colorectal carcinoma

et al. 2013

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G-protein-coupled receptor 120 (GPR120) functions as a receptor for unsaturated long-chain free fatty acids and has an important role in regulating lipid and glucose metabolism. However, a role for GPR120 in the development of tumors has not yet been clarified. Here, we show that GPR120 signaling promotes angiogenic switching and motility of human colorectal carcinoma (CRC) cells. We show that the expression of GPR120 is significantly induced in CRC tissues and cell lines, which is associated with tumor progression. Activation of GPR120 signaling in human CRC promotes angiogenesis in vitro and in vivo, largely by inducing the expression and secretion of proangiogenic mediators such as vascular endothelial growth factor (VEGF), interleukin-8 and cyclooxygenase-2-derived prostaglandin E 2 . The PI3K/Akt-NF-kB pathway is activated by GPR120 signaling and is required for GPR120 signaling-induced angiogenic switching in CRC cells. And, GPR120 activation enhances the motility of CRC cells and induces epithelial-mesenchymal transition. Furthermore, in vivo study shows that activation of GPR120 promotes angiogenesis and tumor growth. Finally, we find that GPR120 expression is positively correlated with VEGF expression and inversely correlated with the epithelial marker E-cadherin in CRC tissues. Collectively, our results demonstrate that GPR120 functions as a tumor-promoting receptor in CRC and, therefore, shows promise as a new potential target for cancer therapeutics.

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“…In native enteroendocrine cells, intracellular levels of Ca 2+ and cAMP are also altered by the activity of a number of G-protein coupled receptors (GPCR's) and nutrient transporters. STC-1 cells have been found to intrinsically express many of these important GPCRs including GPR40 and GPR120 (Tanaka et al 2008 ). Hormone secretion is dependent on GPR40 in native murine I-cells, as linolenic acid induced CCK secretion was absent in cells lacking this receptor (Liou et al 2011b ).…”

Section: Features and Mechanismsmentioning

confidence: 99%

“…Rather, it is GPR120 that appears to play a more important role in fatty acid sensing in STC-1 cells. Fatty acid-induced hormone release is impaired in GPR120 siRNA silencing experiments (Tanaka et al 2008 ). Wang et al .…”

Section: Features and Mechanismsmentioning

confidence: 99%