GPR40:fatty acid activates Gq

Stable Identifier
R-HSA-416530
Type
Reaction [transition]
Species
Homo sapiens
Compartment
plasma membrane, cytosol
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
GPR40:fatty acid activates Gq
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

FFAR1 (GPR40) is a G-protein coupled receptor. Based on studies with inhibitors of G proteins such as pertussis toxin FFAR1 is believed to signal through Gq/11. Binding of free fatty acids by FFAR1 activates the heterotrimeric Gq complex, which then activates Phospholipase C. From experiments in knockout mice it is estimated that signaling through FFAR1 is responsible for about 50% of the augmentation of insulin secretion produced by free fatty acids. The rest of the augmentation is due to metabolism of the free fatty acids within the pancreatic beta cell.

Literature References
PubMed ID Title Journal Year
17130640 Fatty acid signaling in the beta-cell and insulin secretion

Nolan, CJ, Madiraju, MS, Delghingaro-Augusto, V, Peyot, ML, Prentki, M

Diabetes 2006
17395749 GPR40 is necessary but not sufficient for fatty acid stimulation of insulin secretion in vivo

Latour, MG, Alquier, T, Oseid, E, Tremblay, C, Jetton, TL, Luo, J, Lin, DC, Poitout, V

Diabetes 2007
15914509 Oleic acid interacts with GPR40 to induce Ca2+ signaling in rat islet beta-cells: mediation by PLC and L-type Ca2+ channel and link to insulin release

Fujiwara, K, Maekawa, F, Yada, T

Am J Physiol Endocrinol Metab 2005
16081037 Role of GPR40 in fatty acid action on the beta cell line INS-1E

Shapiro, H, Shachar, S, Sekler, I, Hershfinkel, M, Walker, MD

Biochem Biophys Res Commun 2005
18827341 Free fatty acid receptors and drug discovery

Hirasawa, A, Hara, T, Katsuma, S, Adachi, T, Tsujimoto, G

Biol Pharm Bull 2008
12496284 The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids

Briscoe, CP, Tadayyon, M, Andrews, JL, Benson, WG, Chambers, JK, Eilert, MM, Ellis, C, Elshourbagy, NA, Goetz, AS, Minnick, DT, Murdock, PR, Sauls HR, Jr, Shabon, U, Spinage, LD, Strum, JC, Szekeres, PG, Tan, KB, Way, JM, Ignar, DM, Wilson, S, Muir, AI

J Biol Chem 2003
18606873 Glycerolipid metabolism and signaling in health and disease

Prentki, M, Madiraju, SR

Endocr Rev 2008
19398560 The action and mode of binding of thiazolidinedione ligands at free fatty acid receptor 1

Smith, NJ, Stoddart, LA, Devine, NM, Jenkins, L, Milligan, G

J Biol Chem 2009
17101212 Free fatty acids increase cytosolic free calcium and stimulate insulin secretion from beta-cells through activation of GPR40

Schnell, S, Schaefer, M, Schöfl, C

Mol Cell Endocrinol 2007
Participants
Input
Output
Participant Of
hasEvent
Catalyst Activity
Catalyst Activity
Title
guanyl-nucleotide exchange factor activity of FFAR1:FFAR1 ligands [plasma membrane]
Physical Entity
FFAR1:FFAR1 ligands [plasma membrane]
Activity
guanyl-nucleotide exchange factor activity (0005085)
Orthologous Events
GPR40:fatty acid activates Gq (Bos taurus)
GPR40:fatty acid activates Gq (Danio rerio)
GPR40:fatty acid activates Gq (Mus musculus)
GPR40:fatty acid activates Gq (Rattus norvegicus)
GPR40:fatty acid activates Gq (Xenopus tropicalis)
Authored
May, B  (2009-06-08)
Reviewed
Kebede, M  (2009-09-09)
Poitout, V  (2009-09-09)
Madiraju, MS  (2009-10-02)
Created
May, B  (2009-03-29)