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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.
- Source :
-
Diabetes [Diabetes] 2001 Jan; Vol. 50 (1), pp. 12-7. - Publication Year :
- 2001
-
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.
- Subjects :
- Animals
Biological Transport drug effects
Glucose Transporter Type 4
Male
Muscle Fibers, Skeletal metabolism
Rats
Rats, Wistar
Time Factors
Aminoimidazole Carboxamide analogs & derivatives
Aminoimidazole Carboxamide pharmacology
Glucose metabolism
Hypoglycemic Agents pharmacology
Insulin pharmacology
Monosaccharide Transport Proteins metabolism
Muscle Proteins
Muscle, Skeletal metabolism
Ribonucleotides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0012-1797
- Volume :
- 50
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 11147776
- Full Text :
- https://doi.org/10.2337/diabetes.50.1.12