GPR40 Pathway (Homo sapiens)

From WikiPathways

Jump to: navigation, search
1, 21, 21, 21, 21, 21, 21, 21, 21, 2Pancreatic Beta cell Insulin ExocytosisFactin Remodelingenabling insulin exocytosis F-actin filamentsEndoplasmic ReticulumInsulin containing vesiclePLCH1PLCB1PLCD1DAGGPR40GNA11PLCZ1PLCD3Unknown target genesPLCG2PLCG1IP3RPLCB3PLCB2PLCL1PLCE1PKD1inositol-3-phosphateCa2+


Description

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.

Quality Tags

Ontology Terms

 

Bibliography

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

History

View all...
CompareRevisionActionTimeUserComment
107154view14:24, 17 September 2019MaintBotChEBI identifier normalization
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

DataNodes

View all...
NameTypeDatabase referenceComment
Ca2+MetaboliteCHEBI:29108 (ChEBI)
DAGMetaboliteCHEBI:18035 (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-phosphateMetaboliteCHEBI:16595 (ChEBI)

Annotated Interactions

No annotated interactions

Personal tools