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Quantifying gluconeogenesis during fasting

V Chandramouli1, K Ekberg, W C Schumann

  • 1Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4951, USA.

The American Journal of Physiology
|January 22, 1998
PubMed
Summary
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This study shows that deuterium oxide (2H2O) can effectively measure the percentage of glucose production from gluconeogenesis (%GNG) during fasting. %GNG significantly increases over 42 hours of fasting, while the rate of glucose production remains stable.

Area of Science:

  • Metabolic Physiology
  • Biochemistry
  • Endocrinology

Background:

  • Gluconeogenesis is a vital metabolic pathway for maintaining glucose homeostasis, especially during fasting.
  • Accurate quantification of gluconeogenesis' contribution to glucose production (%GNG) is crucial for understanding metabolic adaptation.
  • Previous methods for assessing %GNG have limitations in precision and ease of application.

Purpose of the Study:

  • To evaluate the utility of deuterium oxide (2H2O) for estimating %GNG during progressive fasting in healthy subjects.
  • To determine the time course of %GNG changes throughout a 42-hour fast.
  • To compare 2H2O-based %GNG measurements with estimates derived from [6,6-2H2]glucose infusion.

Main Methods:

  • Healthy subjects ingested 2H2O to achieve specific body water enrichments.

Related Experiment Videos

  • %GNG was calculated using the ratio of deuterium enrichments at C-5 and C-2 of blood glucose, analyzed via hexamethylenetetramine.
  • A subset of subjects received a [6,6-2H2]glucose infusion to measure glucose production rates.
  • Main Results:

    • %GNG increased progressively from 40% at 10 hours to 93% at 42 hours of fasting.
    • Measurements using 2H2O and [6,6-2H2]glucose infusion yielded consistent results for gluconeogenic glucose production (0.99 mg.kg-1.min-1) at 14 and 22 hours.
    • Steady-state enrichment in plasma water and blood glucose was achieved within 1-2 hours post-ingestion of 2H2O.

    Conclusions:

    • 2H2O is a reliable and effective tracer for quantifying %GNG during fasting.
    • %GNG increases significantly with prolonged fasting, indicating a shift towards hepatic glucose production.
    • The rate of glucose production from gluconeogenesis remains relatively constant during the early to mid-fasting periods studied.