title: Chronic treatment with 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside increases insulin-stimulated glucose uptake and GLUT4 translocation in rat skeletal muscles in a fiber type-specific manner.
abstract: Recent studies have demonstrated that chronic administration of AICAR (5-aminoimidazole-4-carboxamide- 1-beta-D-ribofuranoside), an activator of the AMP-activated protein kinase, increases hexokinase activity and the contents of total GLUT4 and glycogen in rat skeletal muscles. To explore whether AICAR also affects insulin-stimulated glucose transport and GLUT4 cell surface content, Wistar rats were subcutaneously injected with AICAR for 5 days in succession (1 mg/g body wt). Maximally insulin-stimulated (60 nmol/l) glucose uptake was markedly increased in epitrochlearis (EPI) muscle (average 63%, P < 0.001, n = 18-19) and in extensor digitorum longus muscle (average 26%, P < 0.001, n = 26-30). In contrast, administration of AICAR did not maximally influence insulin-stimulated glucose transport in soleus muscle. Studies of EPI muscle with the 4,4'-O-[2-[2-[2-[2-[2-[6-(biotinylamino)hexanoyl]amino]ethoxy]ethoxy] ethoxy]-4-(1-azi-2,2,2,-trifluoroethyl)benzoyl]amino-1,3-propanediyl]bis-D-mannose photolabeling technique showed a concomitant increase (average 68%, P < 0.02) in cell surface GLUT4 content after insulin exposure in AICAR-injected rats when compared with controls. In conclusion, 5 days of AICAR administration induces a pronounced fiber type-specific increase in insulin-stimulated glucose uptake and GLUT4 cell surface content in rat skeletal muscle with the greatest effect observed on white fast-twitch glycolytic muscles (EPI). These results are comparable with the effects of chronic exercise training, and it brings the AMP-activated protein kinase into focus as a new interesting target for future pharmacological intervention in insulin-resistant conditions.
authors.affiliation: Medical Department M, Aarhus Kommune-hospital, Denmark.
authors.forename: E S
authors.initials: ES
authors.lastname: Buhl
authors.forename: N
authors.initials: N
authors.lastname: Jessen
authors.forename: O
authors.initials: O
authors.lastname: Schmitz
authors.forename: S B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: O
authors.initials: O
authors.lastname: Pedersen
authors.forename: G D
authors.initials: GD
authors.lastname: Holman
authors.forename: S
authors.initials: S
authors.lastname: Lund
mesh_terms: D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012265:Ribonucleotides / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012265:Ribonucleotides; C495694:Slc2a4 protein, rat; D000620:Aminoimidazole Carboxamide; C031143:AICA ribonucleotide; D005947:Glucose