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Free fatty acids regulate insulin secretion from pancreatic β cells through GPR40

Nature volume 422, pages 173–176 (2003)Cite this article

Abstract

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 β 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 β cells by activating GPR40. Our results indicate that GPR40 agonists and/or antagonists show potential for the development of new anti-diabetic drugs.

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Figure 1: GPR40 mRNA is expressed abundantly in pancreatic β cells.
Figure 2: Induction of [Ca2+]i rise and MAP kinase activation by FFAs in CHO–hGPR40 cells.
Figure 3: Analyses for FFA-induced insulin secretion mechanisms.

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Acknowledgements

We thank Y. Sumino, T. Soda, K. Kato, H. Odaka, F. Itoh, M. Kajino, K. Fukatsu and N. Suzuki for their discussions.

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  1. Yasuaki Itoh and Yuji Kawamata: These authors contributed equally to this work

Authors and Affiliations

  1. Discovery Research Laboratories I, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd, Wadai 10, Tsukuba, Ibaraki, 300-4293, Japan

    Yasuaki Itoh, Yuji Kawamata, Masataka Harada, Makoto Kobayashi, Ryo Fujii, Shoji Fukusumi, Kazuhiro Ogi, Masaki Hosoya, Yasuhiro Tanaka, Hiroshi Uejima, Hideyuki Tanaka, Minoru Maruyama, Rie Satoh, Shoichi Okubo, Hideki Kizawa, Hidetoshi Komatsu, Fumika Matsumura, Yuko Noguchi, Tokuyuki Shinohara, Shuji Hinuma, Yukio Fujisawa & Masahiko Fujino

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Correspondence to Shuji Hinuma.

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Itoh, Y., Kawamata, Y., Harada, M. et al. Free fatty acids regulate insulin secretion from pancreatic β cells through GPR40. Nature 422, 173–176 (2003). https://doi.org/10.1038/nature01478

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