title: 5-amino-imidazole carboxamide riboside increases glucose transport and cell-surface GLUT4 content in skeletal muscle from subjects with type 2 diabetes.
abstract: AMP-activated protein kinase (AMPK) activation by AICAR (5-amino-imidazole carboxamide riboside) is correlated with increased glucose transport in rodent skeletal muscle via an insulin-independent pathway. We determined in vitro effects of insulin and/or AICAR exposure on glucose transport and cell-surface GLUT4 content in skeletal muscle from nondiabetic men and men with type 2 diabetes. AICAR increased glucose transport in a dose-dependent manner in healthy subjects. Insulin and AICAR increased glucose transport and cell-surface GLUT4 content to a similar extent in control subjects. In contrast, insulin- and AICAR-stimulated responses on glucose transport and cell-surface GLUT4 content were impaired in subjects with type 2 diabetes. Importantly, exposure of type 2 diabetic skeletal muscle to a combination of insulin and AICAR increased glucose transport and cell-surface GLUT4 content to levels achieved in control subjects. AICAR increased AMPK and acetyl-CoA carboxylase phosphorylation to a similar extent in skeletal muscle from subjects with type 2 diabetes and nondiabetic subjects. Our studies highlight the potential importance of AMPK-dependent pathways in the regulation of GLUT4 and glucose transport activity in insulin-resistant skeletal muscle. Activation of AMPK is an attractive strategy to enhance glucose transport through increased cell surface GLUT4 content in insulin-resistant skeletal muscle.
authors.affiliation: Department of Surgical Sciences, Karolinska Hospital, Karolinska Institutet, von Eulers väg 4, II tr, SE-171 77 Stockholm, Sweden.
authors.forename: Heikki A
authors.initials: HA
authors.lastname: Koistinen
authors.forename: Dana
authors.initials: D
authors.lastname: Galuska
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Chibalin
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Juleen R
authors.initials: JR
authors.lastname: Zierath
authors.forename: Geoffrey D
authors.initials: GD
authors.lastname: Holman
authors.forename: Harriet
authors.initials: H
authors.lastname: Wallberg-Henriksson
mesh_terms: D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D001692:Biological Transport / Q000187:drug effects; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D066298:In Vitro Techniques; D007328:Insulin / Q000627:therapeutic use; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D012016:Reference Values; D012265:Ribonucleotides / Q000627:therapeutic use*
chemical_list: D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012265:Ribonucleotides; C495692:SLC2A4 protein, human; D000620:Aminoimidazole Carboxamide; C031143:AICA ribonucleotide; D005947:Glucose