The effect of endurance swim training (3 hours per day, 5 days/week, for 10 weeks) on hepatic glucose production (HGP) in liver perfused in situ for 60 minutes with glucagon and insulin was studied in Sprague-Dawley rats. The experiments were performed in fed rats and in rats fasted for 24 hours, but with lactate (8 mmol/L) added to the perfusion medium. Liver glycogen content was significantly lower in fasted than fed rats (fasted untrained and trained: 14 +/- 4 and 11 +/- 3 micromol glycosyl U/g of liver wet weight (WW); fed untrained and trained: 205 +/- 11 and 231 +/- 11 micromol glycosyl U/g of liver WW; not significantly different in trained and untrained rats). Glucagon increased HGP in the 4 experimental groups, but the increases were more rapid and pronounced in trained than in untrained rats in both fed and fasted states. HGP values (area under the curve [AUC] in micromol/g of liver WW) were significantly higher in trained fed (112.1 +/- 7.1 v 85.9 +/- 12.2 in untrained rats) than in trained fasted rats (50.8 +/- 4.4 v 34.7 +/- 3.6 in untrained rats). When compared with untrained rats, the total amount of glucose released by the liver in response to glucagon in trained rats was approximately 30% higher in the fed state and approximately 45% larger in the fasted state. These results indicate that endurance training increases the response of both glycogenolysis and gluconeogenesis to glucagon.

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