ROLE OF GLUTAMINE AS A GLUCOSE PRECURSOR IN FASTING HUMANS

Recently, significant incorporation of labeled carbon into plasma gluc ose was documented during infusion of C-14-labeled glutamine in postab sorptive humans. Such labeling of plasma glucose can occur as a result of two different processes: either 1) through incorporation of glutam ine carbon into glucose via glutamine entering Krebs cycle at alpha-ke toglutarate or 2) through simple fixation of labeled CO2 resulting fro m oxidation of labeled glutamine. Therefore, these studies were design ed to determine 1) whether glutamine contributes carbon to gluconeogen esis other than through mere CO2 fixation, and, if so, 2) whether the apparent transfer of carbon from glutamine to glucose increases with f asting. Fight healthy adults were studied on two consecutive days: onc e after an overnight (18-h) fast and again on the second day of fastin g (42-h fast). On each study day, subjects received a simultaneous 5-h infusion of D-[6,6-H-2(2)]glucose, L-[3,4-C-13(2)]glutamine, and L-[1 -C-14]leucine. Apparent rates of incorporation of glutamine carbon int o glucose were estimated from the appearance of C-13 into plasma gluco se; glucose and glutamine production rates (appearance rate [R-a]) wer e determined from plasma [H-2(2)]glucose and [C-13(2)]glutamine enrich ments, respectively. The appearance of C-14 into plasma glucose was us ed to correct the measured rates of carbon transfer from glutamine to glucose as a result of CO2 fixation. We observed that of the apparent contribution of labeled glutamine to gluconeogenesis, only 4% occurred as a result of fixation of labeled CO2, while 96% seemed to occur thr ough other routes. We also observed that between 18 and 42 h of fastin g, 1) the relative contribution of protein breakdown to glutamine prod uction was enhanced, while that of de novo synthesis declined; 2) the apparent contribution of glutamine to glucose production rose from 8 /- 1 to 16 +/- 3% of overall glucose R-a; and 3) the relative apparent contribution of glutamine to gluconeogenesis remained constant. From the current data, it cannot be ascertained to what extent the apparent carbon transfer from glutamine to glucose represents a true contribut ion of glutamine to gluconeogenesis or mere carbon exchange between th e trichloroacetic acid cycle and the gluconeogenic pathway. These find ings are nevertheless compatible with a role of glutamine as a signifi cant precursor of glucose in fasting humans.