Chronic treatment with 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside increases insulin-stimulated glucose uptake and GLUT4 translocation in rat skeletal muscles in a fiber type-specific manner

E S Buhl, N Jessen, O Schmitz, S B Pedersen, O Pedersen, G D Holman, S Lund

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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] ethoxyl-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.
Original languageEnglish
Pages (from-to)12-17
Number of pages6
JournalDiabetes
Volume50
Issue number1
DOIs
Publication statusPublished - 2001

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Aminoimidazole Carboxamide
Skeletal Muscle
Insulin
Glucose
Muscles
AMP-Activated Protein Kinases
Hexokinase
Mannose
Glycogen
4-aminoimidazole
Wistar Rats
Pharmacology
Exercise

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Chronic treatment with 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside increases insulin-stimulated glucose uptake and GLUT4 translocation in rat skeletal muscles in a fiber type-specific manner. / Buhl, E S; Jessen, N; Schmitz, O; Pedersen, S B; Pedersen, O; Holman, G D; Lund, S.

In: Diabetes, Vol. 50, No. 1, 2001, p. 12-17.

Research output: Contribution to journalArticle

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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] ethoxyl-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.",
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T1 - Chronic treatment with 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside increases insulin-stimulated glucose uptake and GLUT4 translocation in rat skeletal muscles in a fiber type-specific manner

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AU - Jessen, N

AU - Schmitz, O

AU - Pedersen, S B

AU - Pedersen, O

AU - Holman, G D

AU - Lund, S

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AB - 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] ethoxyl-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.

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