GPR40 is expressed in glucagon producing cells and affects glucagon secretion

Flodgren, Erik; Olde, Björn; Meidute-Abaraviciene, Sandra; Winzell, Maria Sörhede; Åhrén, Bo; Salehi, Albert

doi:10.1016/j.bbrc.2006.12.193

Cited by 95 publications

(67 citation statements)

References 20 publications

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“…The antibody did not co-localise with anti-glucagon staining suggesting that GPR40 may not be expressed on α-cells. A similar conclusion had already been drawn on the basis of in situ hybridisation analysis of rat islet sections (where labelling of β-cells was evident and α-cells appeared negative [27]) but this view contrasts sharply with the findings of Flodgren et al [28] who used a different antiserum to GPR40 to reveal the presence of this receptor on α-cells in mouse pancreas. Clearly, further work is required to clarify the situation and to establish whether species differences might account for the divergent results obtained to date for expression of GPR40 in α-cells.…”

Section: Expression Of Gpr40supporting

confidence: 59%

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: Expression Of Gpr40supporting

confidence: 59%

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

Morgan¹,

Dhayal²

2009

Biochemical Pharmacology

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“…however, since it was demonstrated that GRP40 receptors are identified in glucagon-producing clonal α cells and in mouse α cells (Flodgren et al, 2007).…”

Section: Gpr40mentioning

confidence: 99%

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

Winzell

Åhrén

2007

Pharmacology & Therapeutics

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161

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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

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“…These results suggest that FFA1 acts as a receptor for fatty acid-induced insulin secretion. As well as -cells, FFA1 is also reported to be present in -cells (18). Moreover, FFA1 expression has been detected in various pancreas-derived cell lines, including MIN6, -TC-3, HIT-T15 and INS-1E (4,27,30,52).…”

Section: Tissue Distribution Free Fatty Acid Receptor 1 (Ffa1)mentioning

confidence: 97%