A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs

Kotarsky, Knut; Nilsson, Niclas; Flodgren, Erik; Owman, Christer; Olde, Björn

doi:10.1016/s0006-291x(02)03064-4

Cited by 322 publications

(320 citation statements)

References 27 publications

Supporting

Mentioning

303

Contrasting

Unclassified

Order By: Relevance

“…GPR40 is abundantly expressed in murine pancreatic beta cells [3,7] where it mediates the fatty acid-induced augmentation of GSIS in vitro [6]. Long-chain fatty acids act as ligands for human GPR40 in vitro [3,7,23].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Expression of the gene for a membrane-bound fatty acid receptor in the pancreas and islet cell tumours in humans: evidence for GPR40 expression in pancreatic beta cells and implications for insulin secretion

et al. 2006

View full text Add to dashboard Cite

Aims/hypothesis G protein-coupled receptor 40 (GPR40) is abundantly expressed in pancreatic beta cells in rodents, where it facilitates glucose-induced insulin secretion in response to mid-to long-chain fatty acids in vitro. However, GPR40 gene expression in humans has not been fully investigated, and little is known about the physiological and pathophysiological roles of GPR40 in humans. The aim of this study, therefore, was to examine GPR40 expression and its clinical implications in humans. Methods: GPR40 mRNA expression in the human pancreas, pancreatic islets and islet cell tumours was analysed using TaqMan PCR. Results: GPR40 mRNA was detected in all human pancreases collected intraoperatively. It was enriched approximately 20-fold in isolated islets freshly prepared from the pancreases of the same individuals. The estimated mRNA copy number for the GPR40 gene in pancreatic islets was comparable to those for genes encoding sulfonylurea receptor 1, glucagon-like peptide 1 receptor and somatostatin receptors, all of which are known to be expressed abundantly in the human pancreatic islet. A large amount of GPR40 mRNA was detected in insulinoma tissues, whereas mRNA expression was undetectable in glucagonoma or gastrinoma. The GPR40 mRNA level in the pancreas correlated with the insulinogenic index, which reflects beta cell function (r=0.82, p=0.044), but not with glucose levels during the OGTT, the insulin area under the OGTT curve or the index for the homeostasis model assessment of insulin resistance (HOMA-IR). Conclusions/interpretation The present study provides evidence for GPR40 gene expression in pancreatic beta cells and implicates GPR40 in insulin secretion in humans.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Several investigators have recently demonstrated that fatty acids act as ligands for membrane-bound G-proteincoupled receptors such as GPR40 [3,6,7], GPR41, GPR43 [8,9] and GPR120 [10]. GPR40 is preferentially expressed in pancreatic beta cells in rodents and augments GSIS after acute exposure to mid-and long-chain fatty acids [6].…”

Section: Introductionmentioning

confidence: 99%

Expression of the gene for a membrane-bound fatty acid receptor in the pancreas and islet cell tumours in humans: evidence for GPR40 expression in pancreatic beta cells and implications for insulin secretion

et al. 2006

View full text Add to dashboard Cite

show abstract

“…7 Thus, activation of GPR120 should result in an increase in the intracellular Ca 2 þ ([Ca 2 þ ]i) levels, an action mediated via Gaq/11. 10,12,13 To determine whether GPR120 in CRC cells could respond to GW9508 stimulation, we examined the effects of GW9508 on the concentration of [Ca 2 þ ]i response by using [Ca 2 þ ]i staining. GW9508 stimulation induced a specific rise in [Ca 2 þ ]i, which was completely abrogated by shRNA-mediated knockdown of GPR120 (Figure 2c), suggesting that these effects were mediated through the activation of GPR120.…”

Section: Gpr120 Is Induced In Human Crc Tissues and Its Expression Ismentioning

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

View full text Add to dashboard Cite

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.

show abstract

“…An insulinotropic action of FFAs through GPCR was first proposed for GPR40, the activation of which stimulates insulin secretion. (Briscoe et al, 2003;Itoh et al, 2003;Kotarsky et al, 2003). Also GPR41 and GPR43 are fatty-acid-binding GPCRs and might contribute (Brown et al, 2005;Covington et al, 2006).…”

Section: Lipid-binding Gpcrsmentioning

confidence: 99%

“…Also GPR41 and GPR43 are fatty-acid-binding GPCRs and might contribute (Brown et al, 2005;Covington et al, 2006). GPR40 has long-chain FFAs (>C12) as activating ligands (Itoh et al, 2003;Kotarsky et al, 2003), while GPR41 and 43 are activated by short-chain FFAs (<C6) (Brown et al, 2003). Recently, also GRP119 was identified in islets where it might be involved in the FFA-induced insulin secretion (Chu et al, 2007).…”

Section: Lipid-binding Gpcrsmentioning

confidence: 99%

G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes

Winzell

Åhrén

2007

Pharmacology & Therapeutics

161

View full text Add to dashboard Cite

Islet function is regulated by a number of different signals. A main signal is generated by glucose, which stimulates insulin secretion and inhibits glucagon secretion. The glucose effects are modulated by many factors, including hormones, neurotransmitters and nutrients. Several of these factors signal through guanine nucleotide-binding protein (G-protein) coupled receptors (GPCRs). Examples of islet GPCRs are GPR40 and GPR119, which are GPCRs with fatty acids as ligands, the receptors for the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), the receptors for the islet hormones glucagon and somatostatin, the receptors for the classical neurotransmittors

show abstract

A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs

Cited by 322 publications

References 27 publications

Expression of the gene for a membrane-bound fatty acid receptor in the pancreas and islet cell tumours in humans: evidence for GPR40 expression in pancreatic beta cells and implications for insulin secretion

Expression of the gene for a membrane-bound fatty acid receptor in the pancreas and islet cell tumours in humans: evidence for GPR40 expression in pancreatic beta cells and implications for insulin secretion

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

G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes

Contact Info

Product

Resources

About