GPR40 Pathway (Homo sapiens)

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1, 21, 21, 21, 21, 21, 21, 21, 21, 2 F-actin filamentsInsulin containing vesiclePancreatic Beta cellFactin Remodelingenabling insulin exocytosisEndoplasmic Reticulum Insulin ExocytosisPLCG1PLCG2IP3RPLCE1PLCH1PLCB3inositol-3-phosphatePLCD3DAGPLCB2PLCB1Unknown target genesPKD1GPR40GNA11PLCZ1PLCL1Ca2+PLCD1


G-protein-coupled receptor GPR40 (also known as Free fatty acid receptor 1(FFAR1)) is a seven trans-membrane domain receptor which is predominantly expressed in pancreatic beta cells. It plays an essential role in fatty acid ampli�cation of glucose induced insulin secretion. GPR40 agonists are in second phase of preclinical trials for treatment of diabetes because of their role in improved glucose control.

Binding of free fatty acids to GPR40 initiates a downstream signaling cascade which involves activation of a transducer protein “guanine nucleotide-binding protein subunit alpha-11� (GNA11). Next phospholipase c (PLC) hormone is activated which hydrolyzes membrane phospholipids (such as phosphatidylinositol-4-5-biphosphate) into second messenger molecules inositol-1-4-5-trophosphate (IP3) and Diacylglycerol (DAG). IP3 initiates calcium efflux from endoplasmic reticulum and increase intracellular calcium concentration. Increased intracellular calcium concentration is involved in activating the insulin exocytosis machinery. DAG on the other hand activates PKD1. PKD1 initiates F-actin remodeling and supports second phase of insulin exocytosis.

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Ontology Terms



  1. Mancini AD, Poitout V; ''The fatty acid receptor FFA1/GPR40 a decade later: how much do we know? Mancini AD1, Poitout V.''; , 2013 PubMed
  2. Poitout V, Lin DC; ''Modulating GPR40: therapeutic promise and potential in diabetes''; , 2013 PubMed


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96485view16:36, 15 March 2018Fehrhartfixed connection
94758view15:41, 5 October 2017Mkutmonfix unconnected lines
91307view18:43, 26 January 2017KhanspersModified title
91076view20:35, 30 December 2016AlexanderPicoOntology Term : 'insulin secretion pathway' added !
91075view20:34, 30 December 2016AlexanderPicoOntology Term : 'G protein mediated signaling pathway' added !
91074view20:29, 30 December 2016AlexanderPicoManually fixed literature reference
91064view12:24, 29 December 2016EgonwSmall fix in one of the IDs.
91057view22:56, 27 December 2016SiddiqaOntology Term : 'signaling pathway' added !
91056view22:54, 27 December 2016SiddiqaModified description
91055view22:45, 27 December 2016SiddiqaNew pathway

External references


View all...
NameTypeDatabase referenceComment
Ca2+Metabolite29108 (ChEBI)
DAGMetabolite18035 (ChEBI)
GNA11GeneProductENSG00000088256 (Ensembl)
GPR40GeneProductENSG00000126266 (Ensembl)
IP3RGeneProductENSG00000096433 (Ensembl)
PKD1GeneProductENSG00000008710 (Ensembl)
PLCB1GeneProductENSG00000182621 (Ensembl)
PLCB2GeneProductENSG00000137841 (Ensembl)
PLCB3GeneProductENSG00000149782 (Ensembl)
PLCD1GeneProductENSG00000187091 (Ensembl)
PLCD3GeneProductENSG00000161714 (Ensembl)
PLCE1GeneProductENSG00000138193 (Ensembl)
PLCG1GeneProductENSG00000124181 (Ensembl)
PLCG2GeneProductENSG00000197943 (Ensembl)
PLCH1GeneProductENSG00000114805 (Ensembl)
PLCL1GeneProductENSG00000115896 (Ensembl)
PLCZ1GeneProductENSG00000139151 (Ensembl)
Unknown target genesGeneProduct
inositol-3-phosphateMetabolite16595 (ChEBI)

Annotated Interactions

No annotated interactions

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