Non-invasive tracing of liver intermediary metabolism in normal subjects and in moderately hyperglycaemic NIDDM subjects. Evidence against increased gluconeogenesis and hepatic fatty acid oxidation in NIDDM.
To test whether gluconeogenesis is increased in non-insulin-dependent diabetic (NIDDM) patients we infused (post-absorptive state) healthy subjects and NIDDM patients with [6,6-2H2]glucose (150 min) and [3-13C]lactate (6 h). Liver glutamine was sampled with phenylacetate and its labelling pattern determined (mass spectrometry) after purification of the glutamine moiety of urinary phenylacetylglutamine. After correction for 13CO2 re-incorporation (control test with NaH13CO3 infusion) this pattern was used to calculate the dilution factor (F) in the hepatic oxaloacetate pool and fluxes through liver Krebs cycle. NIDDM patients had increased lactate turnover rates (16.18+/-0.92 vs 12.14+/-0.60 micromol x kg(-1) x min(-1), p < 0.01) and a moderate rise in glucose production (EGP) (15.39+/-0.87 vs 12.52+/-0.28 micromol x kg(-1) x min(-1) , p = 0.047). Uncorrected contributions of gluconeogenesis to EGP were 31+/-3 % (control subjects) and 17+/-2 % (NIDDM patients). F was comparable (1.34+/-0.02 and 1.39 0.09, respectively) and the corrected percent and absolute contributions of gluconeogenesis were not increased in NIDDM (25+/-3 % and 3.8+/-O.5 micromol x kg(1) x min[-1]) compared to control subjects (41+/-3 % and 5.1+/-0.4 micromol x kg(-1) x min(-1]). The calculated pyruvate carboxylase over pyruvate dehydrogenase activity ratio was comparable (12.1+/-2.6 vs 11.2+/-1.4). Lastly hepatic fatty oxidation, as estimated by the model, was not increased in NIDDM (1.8+/-0.4 vs 1.6+/-0.1 micromol x kg(-1) x min[-1]). In conclusion, in the patients studied we found no evidence of increased hepatic fatty oxidation, or, despite the increased lactate turnover rate, an increased gluconeogenesis.
Diraison
F
F
Laboratoire de Physiopathologie Métabolique et Rénale, Faculté de Médecine R. Laennec, Lyon, France.
Large
V
V
Brunengraber
H
H
Beylot
M
M
D000328:Adult; D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002247:Carbon Isotopes; D019343:Citric Acid / Q000378:metabolism; D002952:Citric Acid Cycle; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005943:Gluconeogenesis; D006801:Humans; D007201:Indicator Dilution Techniques; D007700:Kinetics; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010728:Phosphoenolpyruvate / Q000378:metabolism; D011766:Pyruvate Carboxylase / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D019289:Pyruvic Acid / Q000097:blood / Q000378:metabolism
D001786:Blood Glucose; D002247:Carbon Isotopes; D005227:Fatty Acids; D011768:Pyruvate Dehydrogenase Complex; D019343:Citric Acid; D019344:Lactic Acid; D010728:Phosphoenolpyruvate; D019289:Pyruvic Acid; D011766:Pyruvate Carboxylase; D000409:Alanine