Reactome | Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion

Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion

Stable Identifier

R-HSA-434316

DOI

10.3180/R-HSA-434316.7

Type

Pathway

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion

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Fatty acids augment the glucose triggered secretion of insulin through two mechanisms: intracellular metabolism and activation of FFAR1 (GPR40), 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, producing inositol 1,4,5-trisphosphate and eventually causing the release of intracellular calcium into the cytosol. 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.

Literature References

PubMed ID	Title	Journal	Year
16289108	GPR40 gene expression in human pancreas and insulinoma Tomita, T, Masuzaki, H, Noguchi, M, Iwakura, H, Fujikura, J, Tanaka, T, Ebihara, K, Kawamura, J, Komoto, I, Kawaguchi, Y, Fujimoto, K, Doi, R, Shimada, Y, Hosoda, K, Imamura, M, Nakao, K	Biochem Biophys Res Commun	2005
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
12565875	A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs Kotarsky, K, Nilsson, NE, Flodgren, E, Owman, C, Olde, B	Biochem Biophys Res Commun	2003
12629551	Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40 Itoh, Y, Kawamata, Y, Harada, M, Kobayashi, M, Fujii, R, Fukusumi, S, Ogi, K, Hosoya, M, Tanaka, Y, Uejima, H, Tanaka, H, Maruyama, M, Satoh, R, Okubo, S, Kizawa, H, Komatsu, H, Matsumura, F, Noguchi, Y, Shinohara, T, Hinuma, S, Fujisawa, Y, Fujino, M	Nature	2003
19758793	G-protein-coupled receptor 40 (GPR40) expression and its regulation in human pancreatic islets: The role of type 2 diabetes and fatty acids Del Guerra, S, Bugliani, M, D'Aleo, V, Del Prato, S, Boggi, U, Mosca, F, Filipponi, F, Lupi, R	Nutr Metab Cardiovasc Dis	2009
18606873	Glycerolipid metabolism and signaling in health and disease Prentki, M, Madiraju, SR	Endocr Rev	2008
19401434	Overexpression of GPR40 in pancreatic beta-cells augments glucose-stimulated insulin secretion and improves glucose tolerance in normal and diabetic mice Nagasumi, K, Esaki, R, Iwachidow, K, Yasuhara, Y, Ogi, K, Tanaka, H, Nakata, M, Yano, T, Shimakawa, K, Taketomi, S, Takeuchi, K, Odaka, H, Kaisho, Y	Diabetes	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