Mechanisms underlying impaired GLUT-4 translocation in glycogen-supercompensated muscles of exercised rats

We previously found that feeding rats a high-carbohydrate diet after exerci se, with muscle glycogen supercompensation, results in a decrease in insuli n responsiveness so severe that it masks the effect of a training-induced t wofold increase in GLUT-4 on insulin-stimulated muscle glucose transport. O ne purpose of this study was to determine whether insulin signaling is impa ired. Maximally insulin-stimulated phosphatidylinositol (PI) 3-kinase activ ity was not significantly reduced, whereas protein kinase B (PKB) phosphory lation was similar to 50% lower (P< 0.01) in muscles of chow-fed, than in t hose of fasted, exercise-trained rats. Our second purpose was to determine whether contraction-stimulated glucose transport is also impaired. The stim ulation of glucose transport and the increase in cell surface GLUT-4 induce d by contractions were both decreased by <similar to>65% in glycogen-superc ompensated muscles of trained rats. The contraction-stimulated increase in AMP kinase activity, which has been implicated in the activation of glucose transport by contractions, was similar to 80% lower in the muscles of the fed compared with the fasted rats 18 h after exercise. These results show t hat both the insulin- and contraction-stimulated pathways for muscle glucos e transport activation are impaired in glycogen-supercompensated muscles an d provide insight regarding possible mechanisms.