INCREASED HEPATIC GLUCOSE-PRODUCTION RESPONSE TO GLUCAGON IN TRAINED SUBJECTS

This study was designed to characterize the impact of endurance traini ng on the hepatic response to glucagon. We measured the effect of gluc agon oh hepatic glucose production (HGP) in resting trained (n = 8) an d untrained (n = 8) healthy male subjects (maximal rate of O-2 consump tion: 65.9 +/- 1.6 vs. 46.8 +/- 0.6 ml O-2 . kg(-1) . min(-1), respect ively, P < 0.001). Endogenous insulin and glucagon were suppressed by somatostatin (somatotropin release-inhibiting hormone) infusion (450 m u g/h) over 4 h. Insulin (0.15 mU . kg(-1) . min(-1)) was infused thro ughout the study, and glucagon (1.5 ng . kg(-1) . min(-1)) was infused over the last 2 h. During the latter period, plasma glucagon and insu lin remained constant at 138.2 +/- 3.1 vs. 145.3 +/- 2.1 ng/l and at 9 5.5 +/- 4.5 vs. 96.2 +/- 1.9 pmol/l in trained and untrained subjects, respectively. Plasma glucose increased and peaked at 11.4 +/- 1.1 mmo l/l in trained subjects and at 8.9 +/- 0.8 mmol/l in untrained subject s (P < 0.001). During glucagon stimulation, the mean increase in HGP a rea under the curve was 15.8 +/- 2.8 mol . kg(-1) . min(-1) in trained subjects compared with 7.4 +/- 1.6 mol . kg(-1) . min(-1) in untraine d subjects (P < 0.01) over the first hour and declined to 6.8 +/- 2.8 and 4.9 +/- 1.4 mol . kg(-1) . min(-1) during the second hour. In conc lusion, these observations indicate that endurance training is associa ted with an increase in HGP in response to physiological levels of glu cagon, thus suggesting an increase in hepatic glucagon sensitivity.