title: Globular adiponectin stimulates glucose transport in type 2 diabetic muscle.
abstract: BACKGROUND
  Adiponectin acts as an insulin sensitizer in rodent models. The direct effect of adiponectin in intact type 2 diabetic muscle is unknown. We examined whether adiponectin stimulates glucose transport in isolated skeletal muscle strips from type 2 diabetic men.
  
  
  METHODS
  We obtained open muscle biopsies from 12 men with type 2 diabetes (56 +/- 1 years, 30.5 +/- 1.1 kg/m(2)), and from 15 non-diabetic men (59 +/- 1 years, 28.0 +/- 1.0 kg/m(2)). Skeletal muscle strips were isolated and exposed to globular adiponectin (2.5 microg/mL), insulin (120 nM) and/or AICAR (1 mM) in vitro for 1 h. Glucose transport was analysed by accumulation of intracellular 3-O-methyl [(3)H] glucose, phosphorylation of Akt-Ser(473) and Akt-Thr(308) was determined using phosphospecific antibodies, and adiponectin receptor 1 and 2 content was measured using specific antibodies.
  
  
  RESULTS
  Globular adiponectin increased glucose transport rate by 1.3-fold (P < 0.01) in type 2 diabetic, but not in non-diabetic muscle. Insulin-stimulated glucose transport rate was unaltered by exposure to globular adiponectin in either group. AICAR increased glucose transport and enhanced insulin-stimulated glucose transport in type 2 diabetic and non-diabetic muscles. Insulin-stimulated phosphorylation of Akt-Ser(473) or Akt-Thr(308) was comparable in type 2 diabetic and non-diabetic muscles, and unaltered by the addition of globular adiponectin in either group. Adiponectin receptor expression was similar in skeletal muscle from type 2 diabetic and non-diabetic men.
  
  
  CONCLUSIONS
  Globular adiponectin directly increases glucose transport in skeletal muscle from type 2 diabetic patients. This may occur via Akt-independent signalling routes.
authors.affiliation: Department of Medicine, Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Kuoppamaa
authors.forename: Paulina
authors.initials: P
authors.lastname: Skrobuk
authors.forename: Maarit
authors.initials: M
authors.lastname: Sihvo
authors.forename: Anne
authors.initials: A
authors.lastname: Hiukka
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Chibalin
authors.forename: Juleen R
authors.initials: JR
authors.lastname: Zierath
authors.forename: Heikki A
authors.initials: HA
authors.lastname: Koistinen
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D052242:Adiponectin / Q000502:physiology*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000096:biosynthesis; D012265:Ribonucleotides / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D020690:GTPase-Activating Proteins; D007328:Insulin; D054419:Receptors, Adiponectin; D012265:Ribonucleotides; C518767:TBC1D4 protein, human; D000620:Aminoimidazole Carboxamide; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D000263:Adenylate Kinase; C031143:AICA ribonucleotide; D005947:Glucose