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 F
  • Itoh Y
  • Kawamata Y
 et al. 
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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.

Author-supplied keywords

  • *Receptors
  • Animals
  • CHO Cells
  • Calcium
  • Calcium Signaling
  • Calcium Signaling/drug effects
  • Calcium Signaling: drug effects
  • Calcium/metabolism
  • Calcium: metabolism
  • Cell Surface
  • Cell Surface/agonists/antagonists &
  • Cell Surface: agonists
  • Cell Surface: antagonists & inhibitors
  • Cell Surface: genetics
  • Cell Surface: metabolism
  • Cricetinae
  • Enzyme Activation
  • Enzyme Activation/drug effects
  • Enzyme Activation: drug effects
  • Fatty Acids
  • G-Protein-Coupled
  • Glucose
  • Glucose/pharmacology
  • Glucose: pharmacology
  • Hamsters
  • Haplorhini
  • Human
  • Humans
  • Insulin
  • Insulin/*secretion
  • Insulin: secretion
  • MAP Kinase Signaling System
  • MAP Kinase Signaling System/drug effects
  • MAP Kinase Signaling System: drug effects
  • Male
  • Messenger
  • Messenger/genetics/metabolism
  • Messenger: genetics
  • Messenger: metabolism
  • Mice
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases/metabolism
  • Mitogen-Activated Protein Kinases: metabolism
  • Molecular Sequence Data
  • Nonesterified
  • Nonesterified/*pharmacology
  • Nonesterified: pharmacology
  • Pancreas
  • Pancreas/cytology/*drug effects/metabolism/*secret
  • Pancreas: cytology
  • Pancreas: drug effects
  • Pancreas: metabolism
  • Pancreas: secretion
  • RNA
  • Rats
  • Receptors
  • Small Interfering
  • Small Interfering/genetics/metabolism
  • Small Interfering: genetics
  • Small Interfering: metabolism
  • Transfection
  • Wistar
  • inhibitors/genetics/*metabolism

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Authors

  • Fujino M. 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

  • Yasuaki Itoh

  • Yuji Kawamata

  • Masataka Harada

  • Makoto Kobayashi

  • Ryo Fujii

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