ESTIMATION OF GLUCOSE-ALANINE-LACTATE-GLUTAMINE CYCLES IN POSTABSORPTIVE HUMANS - ROLE OF SKELETAL-MUSCLE

To evaluate transfer of carbon between plasma glucose and plasma alanine (glucose-alanine cycle) and lactate (Cori cycle), to assess the contribution of skeletal muscle to these cycles, and to determine whether a glucose-glutamine cycle exists in postabsorptive humans, we infused 11 normal overnight-fasted volunteers with [2-H-3]glucose, [6-C-14]glucose, and [3-C-13]alanine to isotopic steady state and in 7 of these simultaneously measured forearm net balance, uptake, and release of labeled and unlabeled glucose, lactate, and alanine. We found that 40.9 +/- 3.3, 66.8 +/- 3.2, and 13.4 +/- 1.1%, respectively, of plasma alanine, lactate, and glutamine carbon came from plasma glucose. More plasma glucose was converted to plasma alanine than could be derived from plasma alanine (1.89 +/- 0.20 vs. 1.48 +/- 0.15 mu mol . kg(-1). min(-1), P < 0.001). A similar direction of net carbon flux was found for lactate (8.5 vs. 4.2 mu mol . kg(-1). min(-1)), with only glutamine adding more carbon to plasma glucose than was received from it (1.0 vs. 0.75 mu mol . kg(-1). min(-1)). Skeletal muscle accounted for 50.2 +/- 3.9 and 45.5 +/- 5.7% of the overall appearance of alanine and lactate in plasma and 54.2 +/- 5.4 and 36.4 +/- 4.2% of their respective origins from plasma glucose. Skeletal muscle release of alanine and lactate that had been formed from plasma glucose accounted for 19.1 +/- 2.1 and 48.3 +/- 4.8%, respectively, of muscle glucose uptake and 42.4 +/- 5.5 and 49.9 +/- 5.8% of the overall release of alanine and lactate from muscle. These results demonstrate in postabsorptive humans that a glucose-glutamine cycle, in contrast to the Cori and glucose-alanine cycles, results in a positive transfer of new carbon to the glucose pool and that approximately one-half of plasma alanine and two-thirds of plasma lactate production from plasma glucose occurs in tissues other than skeletal muscle.