title: Cloning of adiponectin receptors that mediate antidiabetic metabolic effects.
abstract: Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30) is a hormone secreted by adipocytes that acts as an antidiabetic and anti-atherogenic adipokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance and type 2 diabetes. Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice. Conversely, adiponectin-deficient mice exhibit insulin resistance and diabetes. This insulin-sensitizing effect of adiponectin seems to be mediated by an increase in fatty-acid oxidation through activation of AMP kinase and PPAR-alpha. Here we report the cloning of complementary DNAs encoding adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) by expression cloning. AdipoR1 is abundantly expressed in skeletal muscle, whereas AdipoR2 is predominantly expressed in the liver. These two adiponectin receptors are predicted to contain seven transmembrane domains, but to be structurally and functionally distinct from G-protein-coupled receptors. Expression of AdipoR1/R2 or suppression of AdipoR1/R2 expression by small-interfering RNA supports our conclusion that they serve as receptors for globular and full-length adiponectin, and that they mediate increased AMP kinase and PPAR-alpha ligand activities, as well as fatty-acid oxidation and glucose uptake by adiponectin.
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Junji
authors.initials: J
authors.lastname: Kamon
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tsuchida
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokomizo
authors.forename: Shunbun
authors.initials: S
authors.lastname: Kita
authors.forename: Takuya
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyagishi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.forename: Masaki
authors.initials: M
authors.lastname: Tsunoda
authors.forename: Koji
authors.initials: K
authors.lastname: Murakami
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ohteki
authors.forename: Shoko
authors.initials: S
authors.lastname: Uchida
authors.forename: Sato
authors.initials: S
authors.lastname: Takekawa
authors.forename: Hironori
authors.initials: H
authors.lastname: Waki
authors.forename: Nelson H
authors.initials: NH
authors.lastname: Tsuno
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shibata
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koyasu
authors.forename: Kazunari
authors.initials: K
authors.lastname: Taira
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
mesh_terms: D052242:Adiponectin; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D003920:Diabetes Mellitus / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D032342:Muscle Cells / Q000378:metabolism; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D011506:Proteins; D034741:RNA, Small Interfering; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse; D005947:Glucose