Effects of exercise and feeding on the hexosamine biosynthetic pathway in rat skeletal muscle

Products of the hexosamine biosynthesis pathway (HSNP) have been implicated in glucose-induced insulin resistance. We measured the major products of HSNP, UDP-N-acetyl hexosamines (UDP-HexNAc), and the activity of L-glutamine: D-fructose-6-phosphate amidotransferase (GFAT, rate-limiting enzyme) in rat hindlimb muscles immediately after exercise and 1, 3, and 16 h postexercise (swimming) in fed and fasted rats and sedentary controls. Muscle glycogen decreased by 50-75% postexercise. In sedentary rats, muscle GFAT activity decreased by approximately 30% (P < 0.002) after an 18-h fast. GFAT activity was not affected by exercise under any condition. Muscle UDP-HexNAc increased approximately 30% postexercise (P < 0.01) in ad libitum-fed but not in fasted rats. UDP-HexNAc remained elevated (approximately 30%, P < 0.002) for 16 h if animals were fed postexercise. Concentrations of UDP-hexoses, GDP-mannose, and UDP were unchanged postexercise. Conclusions are that muscle GFAT activity is regulated by the nutritional state but not by acute exercise. Glucose flux via HNSP may be increased postexercise in muscles of ad libitum-fed rats. Increased HSNP products may serve as negative feedback regulators to limit excessive muscle glycogen deposition postexercise.