Reduced running endurance in gluconeogenesis-inhibited rats.

The functional significance of gluconeogenesis in prolonging endurance during submaximal activity was assessed in untrained and endurance-trained rats. Gluconeogenesis was inhibited at the phosphoenolpyruvate carboxykinase reaction by 3-mercaptopicolinic acid (3-MPA). Endurance was significantly reduced by 3-MPA in untrained (-32%; P less than 0.005) and in trained rats (-26%; P less than 0.001). Metabolic correlates of fatigue were examined in trained rats. At exhaustion, 3-MPA-treated rats had only 3% of resting hepatic glycogen, 46% of resting white quadriceps glycogen, and 37% of resting blood glucose. All of these substrates were at higher levels in sham-injected controls after the same duration of running (130 min). Glycogen levels in red quadriceps, blood lactate levels, and blood glycerol levels were not different between groups. Plasma free fatty acid levels were elevated to the same extent in both groups after 90 min of activity, remained high at 130 min in controls, but had returned to resting levels in the severely hypoglycemic 3-MPA-treated rats at exhaustion. The results indicate that gluconeogenesis is important for maintaining blood glucose levels and for prolonging endurance time during submaximal activity.