CONTRIBUTION OF HEPATIC GLYCOGENOLYSIS TO GLUCOSE-PRODUCTION IN HUMANS IN RESPONSE TO A PHYSIOLOGICAL INCREASE IN PLASMA-GLUCAGON CONCENTRATION

The contribution of net hepatic glycogenolysis to overall glucose prod uction during a physiological increment in the plasma glucagon concent ration was measured in six healthy subjects (18-24 years, 68-105 kg) a fter an overnight fast. Glucagon (similar to 3 ng.kg(-1).min(-1)), som atostatin (0.1 mu g.kg(-1).min(-1)), and insulin (0.9 pmol.kg(-1) min( -1)) were infused for 3 h. Liver glycogen concentration was measured a t 15-min intervals during this period using C-13-labeled nuclear magne tic resonance spectroscopy, and liver volume was assessed hom magnetic resonance images. The rate of net hepatic glycogenolysis was calculat ed horn the decrease in liver glycogen concentration over time, multip lied by the liver volume. The rate of glucose appearance (R(a)) was ca lculated from [3-H-3]glucose turnover data using a two-compartment mod el of glucose kinetics. Plasma glucagon concentration rose from 136 +/ - 18 to 304 +/- 57 ng/l and plasma glucose concentration rose from 5.6 +/- 0.1 to 10.4 +/- 0.9 mmol/l on initiation of the infusions. Mean b aseline R(a) was 11.8 +/- 0.4 mu mol.kg(-1).min(-1), increased rapidly after the beginning of the infusions, reaching its highest value afte r 20-40 min, and returned to baseline by 140 min. Liver glycogen conce ntration decreased almost linearly (from 300 +/- 19 mmol/l liver at ba seline to 192 +/- 20 mmol/l liver at t = 124 min) during 2 h after the beginning of the infusions, and the calculated mean rate of net hepat ic glycogenolysis was 21.7 +/- 3.6 mu mol.kg(-1).min(-1). Mean R(a) du ring the same time period was 22.8 +/- 2.3 mu mol.kg(-1).min(-1). Thus , net hepatic glycogenolysis accounted for 93 +/- 9% of R(a). In concl usion, during the initial response to a physiological increment in pla sma glucagon, 1) net hepatic glycogenolysis accounts for virtually all of the increase in hepatic glucose production, and 2) glucagon's evan escent effect on hepatic glucose production is not caused by depletion of hepatic glycogen stores.