Glucose production, recycling, Cori cycle, and gluconeogenesis in humans: relationship to serum cortisol

Six normal subjects (NL group) and 13 cancer patients (CAI and CAII groups) were fasted overnight and infused with [U-(13)C]glucose (0.016-0.058 mg x min(-1) x kg(-1)). Plasma glucose and lactate were isolated, and mass isotopomer distributions were determined by gas chromatography-mass spectroscopy. Applying equations modified from those previously described [J. A. Tayek and J. Katz. Am. J. Physiol. 270 (Endocrinol. Metab. 33): E709-E717, 1996], we determined glucose production (GP), recycling of glucose carbons, fraction of recycled molecules in blood glucose (Cori cycle), formation of pyruvate from unlabeled carbons, dilution of pyruvate via the tricarboxylic acid cycle and other reactions, and rate of gluconeogenesis. Glucose production was similar in all groups: 2.4 +/- 0.2 mg x min(-1) x kg (-1). The fraction of recycled carbon and of the Cori cycle were elevated in the CAI group vs. the CAII and NL groups: 15 and 33% vs. 7.8 and 19%, respectively (P = 0.01). Gluconeogenesis was 1.9 +/- 0.1, 1.0 +/- 0.1, and 0.83 +/- 0.11 mg x min(-1) x kg(-1) in the CAI, CAII, and NL groups, respectively. In the NL and CAII groups, 20% of GP is via recycling, 20% from unlabeled carbon sources (muscle glycogen, amino acids), and 60% from hepatic glycogenolysis; in the CAI group, 30% is from recycling, 50% from unlabeled carbon, and 20% from glycogen and other sources. Serum cortisol was elevated in the CAI group vs. the CAII group: 11.2 +/- 1.2 vs. 7.7 +/- 1.2 microg/dl (P < 0.05). There was a strong correlation between plasma cortisol and Cori cycle in the NL (r = 0.963) and CAI and CAII groups (r = 0.771). Serum cortisol was directly, and insulin was inversely, correlated with gluconeogenesis in the NL (r2 = 0.967) and CAI and CAII groups (r2 = 0.727). We conclude that whereas the cancer population is heterogeneous with respect to gluconeogenesis, many cancer patients derive their GP predominantly from gluconeogenesis compared with healthy controls, who derive less than one-half of their GP from gluconeogenesis.