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Nature 422, 173-176 (13 March 2003) | doi:10.1038/nature01478; Received 2 January 2003; Accepted 11 February 2003; Published online 23 February 2003

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Free fatty acids regulate insulin secretion from pancreatic bold beta cells through GPR40

Yasuaki Itoh1,2, Yuji Kawamata1,2, Masataka Harada1, Makoto Kobayashi1, Ryo Fujii1, Shoji Fukusumi1, Kazuhiro Ogi1, Masaki Hosoya1, Yasuhiro Tanaka1, Hiroshi Uejima1, Hideyuki Tanaka1, Minoru Maruyama1, Rie Satoh1, Shoichi Okubo1, Hideki Kizawa1, Hidetoshi Komatsu1, Fumika Matsumura1, Yuko Noguchi1, Tokuyuki Shinohara1, Shuji Hinuma1, Yukio Fujisawa1 & Masahiko Fujino1

  1. Discovery Research Laboratories I, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd, Wadai 10, Tsukuba, Ibaraki 300-4293, Japan
  2. These authors contributed equally to this work

Correspondence to: Shuji Hinuma1 Correspondence and requests for materials should be addressed to S.H. (e-mail: Email: Hinuma_Shuji@takeda.co.jp).

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Diabetes, a disease in which carbohydrate and lipid metabolism are regulated improperly by insulin, is a serious worldwide health issue1, 2. Insulin is secreted from pancreatic beta cells in response to elevated plasma glucose, with various factors modifying its secretion3. Free fatty acids (FFAs) provide an important energy source as nutrients, and they also act as signalling molecules in various cellular processes, including insulin secretion4, 5. Although FFAs are thought to promote insulin secretion in an acute phase, this mechanism is not clearly understood6. Here we show that a G-protein-coupled receptor, GPR40, which is abundantly expressed in the pancreas, functions as a receptor for long-chain FFAs. Furthermore, we show that long-chain FFAs amplify glucose-stimulated insulin secretion from pancreatic beta cells by activating GPR40. Our results indicate that GPR40 agonists and/or antagonists show potential for the development of new anti-diabetic drugs.