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1 Medical Research Laboratory and Medical Department M(Endocrinology and Diabetes), Aarhus University Hospital, Aarhus Kommunehospital, Aarhus, Denmark
2 Medical Research Laboratory and Medical Department M(Endocrinology and Diabetes), Aarhus University Hospital, Aarhus Kommunehospital, Aarhus, Denmark; Department of Clinical Pharmacology, University of Aarhus, Aarhus, Denmark
* To whom correspondence should be addressed. E-mail: SL{at}Dadlnet.dk.
Physical activity is known to increase insulin action in skeletal muscle and data have indicated that 5'-AMP-activated protein kinase (AMPK) is involved in the molecular mechanisms behind this beneficial effect. 5-aminoimidazole-4-carboxamide-1-
-D-ribofuranoside (AICAR) can be used as a pharmacological tool to repeatedly activate AMPK, and the objective of this study was to explore whether the increase in insulin stimulated glucose uptake after either long-term exercise or chronic AICAR-administration was followed by fiber-type specific changes in insulin signaling and/or changes in GLUT4-expression. Wistar rats were allocated into three groups: an exercise-group trained on treadmill for 5 days, an AICAR-group exposed to daily subcutaneously injections of AICAR, and a sedentary control-group. AMPK activity, insulin-stimulated glucose transport, insulin signaling, and GLUT4 expression were determined in muscles characterized by different fiber-type compositions. Both exercised and AICAR-injected animals displayed a fiber-type specific increase in glucose transport with the most marked increase in muscles with a high content of type IIb fibers. This increase was accompanied by a concomitant increase in GLUT4 expression. Insulin signaling as assessed by PI3-kinase and PKB/Akt activity was only enhanced after AICAR administration and this in a non fiber-type specific manner. In conclusion, chronic AICAR-administration and long-term exercise both improve insulin stimulated glucose transport in skeletal muscle in a fiber-type specific way and this is associated with an increase in GLUT4 content.
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