title: Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40.
abstract: Diabetes, a disease in which carbohydrate and lipid metabolism are regulated improperly by insulin, is a serious worldwide health issue. Insulin is secreted from pancreatic beta cells in response to elevated plasma glucose, with various factors modifying its secretion. Free fatty acids (FFAs) provide an important energy source as nutrients, and they also act as signalling molecules in various cellular processes, including insulin secretion. Although FFAs are thought to promote insulin secretion in an acute phase, this mechanism is not clearly understood. 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.
authors.affiliation: Discovery Research Laboratories I, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd, Wadai 10, Tsukuba, Ibaraki 300-4293, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Itoh
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kawamata
authors.forename: Masataka
authors.initials: M
authors.lastname: Harada
authors.forename: Makoto
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Ryo
authors.initials: R
authors.lastname: Fujii
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukusumi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ogi
authors.forename: Masaki
authors.initials: M
authors.lastname: Hosoya
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uejima
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Minoru
authors.initials: M
authors.lastname: Maruyama
authors.forename: Rie
authors.initials: R
authors.lastname: Satoh
authors.forename: Shoichi
authors.initials: S
authors.lastname: Okubo
authors.forename: Hideki
authors.initials: H
authors.lastname: Kizawa
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Komatsu
authors.forename: Fumika
authors.initials: F
authors.lastname: Matsumura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Noguchi
authors.forename: Tokuyuki
authors.initials: T
authors.lastname: Shinohara
authors.forename: Shuji
authors.initials: S
authors.lastname: Hinuma
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujisawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Fujino
mesh_terms: D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D000882:Haplorhini; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D014162:Transfection
chemical_list: C473034:FFAR1 protein, human; D005230:Fatty Acids, Nonesterified; C473036:Ffar1 protein, mouse; C473035:G-protein-coupled receptor 40, rat; D007328:Insulin; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose; D002118:Calcium