Glucose production, recycling, cori cycle and gluconeogenesis in
humans with and without cancer: relationship to serum cortisol
concentration.
Tayek, John A., Joseph Katz.
Department of Internal Medicine, Harbor-UCLA Medical Center
APStracts 3:0215E, 1996.
Six normal volunteers and 13 cancer volunteers fasted overnight and
were infused with from 0.015 to 0.050 mg/min/kg of [U-C13 ] glucose.
Plasma glucose and lactate were isolated and mass isotopomer
distributions determined by GC-MS. Applying equations modified from
those previously described (Tayek and Katz, Am. J. Physiol. 270:
E704-E717, 1996), we determined glucose production (GP), recycling of
glucose carbons, the fraction of recycled molecules in blood glucose
(Cori Cycle), the formation of pyruvate from unlabeled carbons, the
dilution of pyruvate via the tricarboxcylic acid (TCA) cycle and
other reaction's, and the rate of gluconeogenesis. We find nine
cancer patients with markedly elevated Cori cycle and gluconeogenesis
(cancer group 1 or CA 1) versus healthy normals, while four cancer
patients (CA 2) resembled healthy normals. We present here results
(meansem) for CA 1, CA 2 and for healthy normals (NL). GP was similar
in the groups and averaged 2.500.19 mg/min/kg for CA 1, 2.450.35 for
CA 2, and 2.350.15 mg/min/kg for NL. Recycling of carbon averaged
151.1% for CA 1, and only 7.8_embed Equation.2 ___0.4% for CA 2 and
7.7_embed Equation.2 ___1% in NL, respectively (p<0.01). Cori
Cycle was 33_embed Equation.2 ___2% in CA 1, 19_embed Equation.2
___1% in CA 2, and 19_embed Equation.2 ___2% in NL (p<0.01).
Gluconeogenesis was 1.93_embed Equation.2 ___0.13 mg/min/kg in CA 1,
and 1.03_embed Equation.2 ___0.04 in CA 2, and 0.83_embed Equation.2
___0.11 in NL (p<0.01). In healthy volunteers and CA 2, 20% of
GP is via recycling, 20% from unlabeled carbon sources (muscle
glycogen, amino acids) and 60% from hepatic glycogenolysis. In CA 1,
30% is from recycling, 50% from unlabeled carbon, and 20% from other
sources. Serum cortisol was elevated in CA 1 (11.2_embed Equation.2
___1.2 ug/d) compared with CA 2 (7.7_embed Equation.2 ___1.2;
p<0.05). There was a strong correlation between plasma
cortisol and Cori Cycle in normals (r=0.963) and in cancer patients
(r=0.771). Serum cortisol was also correlated with gluconeogenesis in
normals (r=0.861) and to a lesser extent in cancer patients (r=0.564,
p<0.05). Cortisol was directly, and insulin inversely,
correlated with gluconeogenesis in normals (r2 = 0.967) and cancer
volunteers (r2=0.727). We conclude that while the cancer population
is heterogeneous in respect to gluconeogenesis, many cancer patients
derive nearly all their GP from gluconeogenesis compared to less than
half in healthy controls.
Received 1 May 1996; accepted in final form 24 September 1996.
APS Manuscript Number E209-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996