EFFECTS OF EXERCISE AND GLYCOGEN DEPLETION ON GLYCONEOGENESIS IN MUSCLE

In the present study, we investigated the hypotheses that I) skeletal muscle glyconeogenesis will increase after exercise, 2) greater changes in glyconeogenesis will be observed after exercise in fast-twitch muscles than in slow-twitch muscles, and 3) glycogen repletion will reduce the rates of glyconeogenesis. Mouse soleus and extensor digitorum longus (EDL) glycogen depots were reduced to the same levels by treadmill exercise (60 min) or epinephrine injection (75 mu g/100 g body wt ip). Untreated animals were used as controls. We were able to prevent glycogen repletion by incubating muscles in vitro with sorbitol (75 mM) and to increase glycogen concentrations in vitro by incubating muscles with glucose (75 mM). The experimental results showed that glyconeogenesis was increased by exercise (EDL, +51%; soleus, +82%) when glycogen levels were kept low. When glycogen depots were increased, the rate of glyconeogenesis was lowered in the exercised EDL (P < 0.05) but not in the soleus (P > 0.05). Reductions in muscle glycogen by epinephrine did not change the rate of glyconeogenesis in EDL, either when glycogen depots were kept low or were repleted (P > 0.05). In contrast, in the soleus, epinephrine-induced reductions in glycogen did stimulate glyconeogenesis (P < 0.05). Analyses in EDL showed that in nonexercised muscles glycogen concentrations were minimally effective in altering the rates of glyconeogenesis. A 30% decrement in glycogen increased glyconeogenesis by 5% in resting muscles, whereas the same decrement increased glyconeogenesis by 51% in exercised muscles. We conclude that in fast-twitch muscle (EDL), which exhibits the greatest rate of glyconeogenesis from lactate, 1) glycogen reduction alone provides a negligible increase in glyconeogenesis, 2) exercise-induced metabolic factors coordinately regulate the enzymatic machinery to stimulate glyconeogenesis, and 3) increasing the concentration of glycogen inhibits exercise-induced increments in glyconeogenesis.