Free fatty acid receptor 1 (FFA1R/GPR40) and its involvement in fatty-acid-stimulated insulin secretion

Salehi, Albert; Flodgren, Erik; Nilsson, Niclas; Jimenez-Feltström, Javier; Miyazaki, Jun‐ichi; Owman, Christer; Olde, Björn

doi:10.1007/s00441-005-0017-z

Cited by 138 publications

(111 citation statements)

References 41 publications

(57 reference statements)

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“…In a recent study of the effects of FFAs on insulin secretion, we found that FFAs exert the stimulatory effect on the beta-cell by hormone like properties, i.e. activating the G-protein coupled receptor 40 (GPR40) [4]. Such a modulatory effect of FFAs, through the GPR40 pathway, on insulin secretion has also been reported by other research groups [2,5].…”

Section: Introductionsupporting

confidence: 74%

“…The GPR40 antibody 5 was raised in rabbit against the C-terminal peptide: NH2-CVTRTQRGTIQK-COOH (Innovagen, Lund, Sweden). The specificity of this antibody was tested in a previous study [4]. For staining of glucagon, islets were incubated with a guinea pig-raised anti-glucagon (1:1000) antibody followed by incubation with a Cy5-conjugated anti-guinea pig IgG antibody (1:150).…”

Section: Confocal Microscopymentioning

confidence: 99%

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GPR40 is expressed in glucagon producing cells and affects glucagon secretion

Flodgren

Olde

Meidute-Abaraviciene

et al. 2007

Biochemical and Biophysical Research Communications

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Section: Introductionsupporting

confidence: 74%

Section: Confocal Microscopymentioning

confidence: 99%

GPR40 is expressed in glucagon producing cells and affects glucagon secretion

Flodgren

Olde

Meidute-Abaraviciene

et al. 2007

Biochemical and Biophysical Research Communications

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“…These events may very well be driven by the increased flux of NEFA that arises in the mice as a consequence of HF feeding. The fact that beta cells express G-protein-coupled receptors that utilise NEFA as ligands, the GPR 40 family [27][28][29], raises the possibility that receptor-mediated events triggered by lipids account, at least partially, for the mitochondrial adaptation. Whereas the physiological role of the GPR 40 receptors is still unresolved, our present findings point to an interesting area of beta cell physiology that could be examined with GPR 40 receptors in mind.…”

Section: Discussionmentioning

confidence: 99%

Enhanced mitochondrial metabolism may account for the adaptation to insulin resistance in islets from C57BL/6J mice fed a high-fat diet

et al. 2006

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Aim/hypothesis Hyperinsulinaemia maintains euglycaemia in insulin-resistant states. The precise cellular mechanisms by which the beta cells adapt are still unresolved. A peripherally derived cue, such as increased circulating fatty acids, may instruct the beta cell to initiate an adaptive programme to maintain glucose homeostasis. When this fails, type 2 diabetes ensues. Because mitochondria play a key role in beta cell pathophysiology, we tested the hypothesis that mitochondrial metabolism is critical for beta cell adaptation to insulin resistance. Methods C57BL/6J mice were given high-fat (HF) diet for 12 weeks. We then analysed islet hormone secretion, metabolism in vivo and in vitro, and beta cell morphology.Results HF diet resulted in insulin resistance and glucose intolerance but not frank diabetes. Basal insulin secretion was elevated in isolated islets from HF mice with almost no additional response provoked by high glucose. In contrast, a strong secretory response was seen when islets from HF mice were stimulated with fuels that require mitochondrial metabolism, such as glutamate, glutamine, alpha-ketoisocaproic acid and succinate. Moreover, while glucose oxidation was impaired in islets from HF mice, oxidation of glutamine and palmitate was enhanced. Ultrastructural analysis of islets in HF mice revealed an accumulation of lipid droplets in beta cells and a twofold increase in mitochondrial area. Conclusions/interpretation We propose that beta cells exposed to increased lipid flux in insulin resistance respond by increasing mitochondrial volume. This expansion is associated with enhanced mitochondrial metabolism as a means of beta cell compensation.

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“…GPR40 is highly expressed in mouse, rat and human pancreatic β cells, and thought to be involved in the regulation of FFA-potentiated glucose-stimulated insulin secretion (Itoh et al, 2003;Salehi et al, 2005;Tomita et al, 2006). In fact, GPR40 has been suggested to mediate the majority of the effects of fatty acids on β cells (Itoh et al, 2003;Salehi et al, 2005).…”

Section: Gpr40mentioning

confidence: 99%

“…In fact, GPR40 has been suggested to mediate the majority of the effects of fatty acids on β cells (Itoh et al, 2003;Salehi et al, 2005).…”

Section: Gpr40mentioning

confidence: 99%

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

Winzell

Åhrén

2007

Pharmacology & Therapeutics

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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Free fatty acid receptor 1 (FFA1R/GPR40) and its involvement in fatty-acid-stimulated insulin secretion

Cited by 138 publications

References 41 publications

GPR40 is expressed in glucagon producing cells and affects glucagon secretion

GPR40 is expressed in glucagon producing cells and affects glucagon secretion

Enhanced mitochondrial metabolism may account for the adaptation to insulin resistance in islets from C57BL/6J mice fed a high-fat diet

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

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