Decreasing intramuscular phosphagen content simultaneously increases plasma membrane FAT/CD36 and GLUT4 transporter abundance.
Decreasing muscle phosphagen content through dietary administration of the creatine analog beta-guanidinopropionic acid (beta-GPA) improves skeletal muscle oxidative capacity and resistance to fatigue during aerobic exercise in rodents, similar to that observed with endurance training. Surprisingly, the effect of beta-GPA on muscle substrate metabolism has been relatively unexamined, with only a few reports of increased muscle GLUT4 content and insulin-stimulated glucose uptake/clearance in rodent muscle. The effect of chronically decreasing muscle phophagen content on muscle fatty acid (FA) metabolism (transport, oxidation, esterification) is virtually unknown. The purpose of the present study was to examine changes in muscle substrate metabolism in response to 8 wk feeding of beta-GPA. Consistent with other reports, beta-GPA feeding decreased muscle ATP and total creatine content by approximately 50 and 90%, respectively. This decline in energy charge was associated with simultaneous increases in both glucose (GLUT4; +33 to 45%, P < 0.01) and FA (FAT/CD36; +28 to 33%, P < 0.05) transporters in the sarcolemma of red and white muscle. Accordingly, we also observed significant increases in insulin-stimulated glucose transport (+47%, P < 0.05) and AICAR-stimulated palmitate oxidation (+77%, P < 0.01) in the soleus muscle of beta-GPA-fed animals. Phosphorylation of AMPK (+20%, P < 0.05), but not total protein, was significantly increased in both fiber types in response to muscle phosphagen reduction. Thus the content of sarcolemmal transporters for both of the major energy substrates for muscle increased in response to a reduced energy charge. Increased phosphorylation of AMPK may be one of the triggers for this response.
Pandke
Kristin E
KE
Dept. of Human Health and Nutritional Sciences, Univ. of Guelph, Guelph, Ontario, Canada N1G 2W1.
Mullen
Kerry L
KL
Snook
Laelie A
LA
Bonen
Arend
A
Dyck
David J
DJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D018955:CD36 Antigens / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D050612:Fatty Acid Transport Proteins / Q000378:metabolism; D005260:Female; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D018763:Muscle Fatigue / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010168:Palmitates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D018955:CD36 Antigens; C008132:Cd36 protein, rat; D050612:Fatty Acid Transport Proteins; D051275:Glucose Transporter Type 4; D006146:Guanidines; D007328:Insulin; D010168:Palmitates; D011422:Propionates; C495694:Slc2a4 protein, rat; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D000263:Adenylate Kinase; D003401:Creatine; C005775:guanidinopropionic acid