Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion

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Homo sapiens
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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

Shimada, Y, Masuzaki, H, Nakao, K, Kawamura, J, Tanaka, T, Fujikura, J, Doi, R, Ebihara, K, Noguchi, M, Fujimoto, K, Imamura, M, Iwakura, H, Komoto, I, Tomita, T, Kawaguchi, Y, Hosoda, K

Biochem Biophys Res Commun 2005
12496284 The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids

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

J Biol Chem 2003
12565875 A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs

Olde, B, Flodgren, E, Owman, C, Kotarsky, K, Nilsson, NE

Biochem Biophys Res Commun 2003
12629551 Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40

Matsumura, F, Shinohara, T, Okubo, S, Tanaka, Y, Komatsu, H, Itoh, Y, Noguchi, Y, Maruyama, M, Kobayashi, M, Kizawa, H, Kawamata, Y, Fujisawa, Y, Hinuma, S, Harada, M, Fujino, M, Uejima, H, Ogi, K, Fujii, R, Hosoya, M, Tanaka, H, Fukusumi, S, Satoh, R

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

Mosca, F, D'Aleo, V, Filipponi, F, Del Guerra, S, Bugliani, M, Lupi, R, Boggi, U, Del Prato, S

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

Esaki, R, Kaisho, Y, Nakata, M, Taketomi, S, Yano, T, Ogi, K, Shimakawa, K, Iwachidow, K, Odaka, H, Takeuchi, K, Yasuhara, Y, Nagasumi, K, Tanaka, H

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

Schöfl, C, Schnell, S, Schaefer, M

Mol Cell Endocrinol 2007
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