GPR40 pathway (WP3958)

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.
last edited

Authors

Siddiqa, Egonw, AlexanderPico, Khanspers, Mkutmon, Fehrhart, MaintBot, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: G protein mediated signaling pathway signaling pathway insulin secretion pathway

Participants

Label Type Compact Identifier
inositol-3-phosphate Metabolite chebi:16595
PLCH1 GeneProduct ensembl:ENSG00000114805
DAG Metabolite chebi:18035
PLCD3 GeneProduct ensembl:ENSG00000161714
PLCG2 GeneProduct ensembl:ENSG00000197943
PKD1 GeneProduct ensembl:ENSG00000008710
IP3R GeneProduct ensembl:ENSG00000096433
PLCD1 GeneProduct ensembl:ENSG00000187091
PLCZ1 GeneProduct ensembl:ENSG00000139151
PLCB1 GeneProduct ensembl:ENSG00000182621
Ca2+ Metabolite chebi:29108
GNA11 GeneProduct ensembl:ENSG00000088256
PLCE1 GeneProduct ensembl:ENSG00000138193
PLCL1 GeneProduct ensembl:ENSG00000115896
PLCB2 GeneProduct ensembl:ENSG00000137841
PLCB3 GeneProduct ensembl:ENSG00000149782
GPR40 GeneProduct ensembl:ENSG00000126266
PLCG1 GeneProduct ensembl:ENSG00000124181
Unknown target genes GeneProduct None

References

  1. Mancini AD, Poitout V. The fatty acid receptor FFA1/GPR40 a decade later: how much do we know? Trends Endocrinol Metab. 2013 Aug;24(8):398–407. PubMed Europe PMC Scholia
  2. Poitout V, Lin DC-H. Modulating GPR40: therapeutic promise and potential in diabetes. Drug Discov Today. 2013 Dec;18(23–24):1301–8. PubMed Europe PMC Scholia