title: A novel insulinotropic mechanism of whole grain-derived γ-oryzanol via the suppression of local dopamine D2receptor signalling in mouse islet.
abstract: OBJECTIVE
  γ-Oryzanol, derived from unrefined rice, attenuated the preference for dietary fat in mice, by decreasing hypothalamic endoplasmic reticulum stress. However, no peripheral mechanisms, whereby γ-oryzanol could ameliorate glucose dyshomeostasis were explored. Dopamine D2receptor signalling locally attenuates insulin secretion in pancreatic islets, presumably via decreased levels of intracellular cAMP. We therefore hypothesized that γ-oryzanol would improve high-fat diet (HFD)-induced dysfunction of islets through the suppression of local D2receptor signalling.
  
  
  METHODS
  Glucose metabolism and regulation of molecules involved in D2receptor signalling in pancreatic islets were investigated in male C57BL/6J mice, fed HFD and treated with γ-oryzanol . In isolated murine islets and the beta cell line, MIN6 , the effects of γ-oryzanol on glucose-stimulated insulin secretion (GSIS) was analysed using siRNA for D2receptors and a variety of compounds which alter D2receptor signalling.
  
  
  RESULTS
  In islets, γ-oryzanol enhanced GSIS via the activation of the cAMP/PKA pathway. Expression of molecules involved in D2receptor signalling was increased in islets from HFD-fed mice, which were reciprocally decreased by γ-oryzanol. Experiments with siRNA for D2receptors and D2receptor ligands in vitro suggest that γ-oryzanol suppressed D2receptor signalling and augmented GSIS.
  
  
  CONCLUSIONS
  γ-Oryzanol exhibited unique anti-diabetic properties. The unexpected effects of γ-oryzanol on D2receptor signalling in islets may provide a novel; natural food-based, approach to anti-diabetic therapy.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), University of the Ryukyus, Okinawa, Japan.
authors.forename: Chisayo
authors.initials: C
authors.lastname: Kozuka
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), University of the Ryukyus, Okinawa, Japan.
authors.forename: Sumito
authors.initials: S
authors.lastname: Sunagawa
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), University of the Ryukyus, Okinawa, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Ueda
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), University of the Ryukyus, Okinawa, Japan.|The Diabetes and Life-Style Related Disease Center, Tomishiro Central Hospital, Okinawa, Japan.
authors.forename: Moritake
authors.initials: M
authors.lastname: Higa
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), University of the Ryukyus, Okinawa, Japan.|Okinawa Daiichi Hospital, Okinawa, Japan.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Ohshiro
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), University of the Ryukyus, Okinawa, Japan.|Tanaka Clinic, Okinawa, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Molecular Anatomy, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Chigusa
authors.initials: C
authors.lastname: Shimizu-Okabe
authors.affiliation: Department of Molecular Anatomy, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Chitoshi
authors.initials: C
authors.lastname: Takayama
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Matsushita
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Ishiuchi
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Tochigi, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakata
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Tochigi, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
authors.affiliation: Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Miyazaki
authors.affiliation: Institute for Genome Research, University of Tokushima, Tokushima, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Oyadomari
authors.affiliation: Department of Cardio-Diabetes Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Shimabukuro
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), University of the Ryukyus, Okinawa, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Masuzaki