DIRECT ASSESSMENT OF LIVER-GLYCOGEN STORAGE BY C-13 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY AND REGULATION OF GLUCOSE-HOMEOSTASIS AFTER A MIXED MEAL IN NORMAL SUBJECTS

Despite extensive recent studies, understanding of the normal postpran dial processes underlying immediate storage of substrate and maintenan ce of glucose homeostasis in humans after a mixed meal has been incomp lete, The present study applied C-13 nuclear magnetic resonance spectr oscopy to measure sequential changes in hepatic glycogen concentration , a novel tracer approach to measure postprandial suppression of hepat ic glucose output, and acetaminophen to trace the pathways of hepatic glycogen synthesis to elucidate the homeostatic adaptation to the fed state in healthy human subjects, After the liquid mixed meal, liver gl ycogen concentration rose from 207 +/- 22 to 316 +/- 19 mmol/liter at an average rate of 0.34 mmol/liter per min and peaked at 318 +/- 31 mi n, falling rapidly thereafter (0.26 mmol/liter per min). The mean incr ement at peak represented net glycogen synthesis of 28.3 +/- 3.7 g (si milar to 19% of meal carbohydrate content). The contribution of the di rect pathway to overall glycogen synthesis was 46 +/- 5 and 68 +/- 8% between 2 and 4 and 4 and 6 h, respectively. Hepatic glucose output wa s completely suppressed within 30 min of the meal, It increased steadi ly from 60 to 255 min from 0.31 +/- 32 to 0.49 +/- 18 mg/kg per min th en rapidly returned towards basal levels (1.90 +/- 0.04 mg/kg per min) . This pattern of change mirrored precisely the plasma glucagon/insuli n ratio, These data provide for the first time a comprehensive picture of normal carbohydrate metabolism in humans after ingestion of a mixe d meal.