The present study was designed to determine the effect of fasting on gluconeogenesis from alanine. This process was measured by combining the infusion of l4C-alanine with the A-V difference technique. Normal subjects were studied after 12 and 48 h of fasting and obese subjects were studied after 18 days of therapeutic starvation. After a 12-h fast the hepatic venous 14C-alanine specific activity was 34% lower than the arterial 14C-alanine specific activity, which was consistent with a dynamic exchange of alanine between the intestine and the plasma and with a net release of unlabeled alanine by the intestine. Under these conditions the net splanchnic alanine uptake (106 μmol/min) would underestimate the actual hepatic extraction of alanine, which could be estimated as at least 147 μmol/min. After 48 h and 18 days of fasting, the 14C-alanine specific activity equaled that in the arterial plasma, indicating cessation of intestinal release of alanine into the portal circulation. Under these circumstances, net splanchnic alanine uptake would equal net hepatic alanine extraction. Thus, actual hepatic alanine ëxtraction rates at 48 h and 18 days of fasting were 134 and 94 μmol/min, respectively.
In the face of a decreasing hepatic alanine extraction with fasting, gluconeogenesis from alanine increased by 100% (from 41 to 82 μmol/min) after 48 h of fasting. After 18 days of starvation 51 /μmol/min of alanine was converted to glucose, a rate still 25% higher than after a 12-h fast.
We concluded: (a) fasting is associated with a gradual decrease in hepatic alanine extraction; (b) however, gluconeogenesis from alanine is increased after 48 h and 18 days of fasting due to a more efficient intrahepatic conversion of alanine to glucose.