Rothman · Science (New York, N.Y.) 1991 · prospective physiological study · n=?

Quantitation of hepatic glycogenolysis and gluconeogenesis in fasting humans with 13C NMR.

Cited 544 times in the scientific literature.

Level 4 - case-series / case-control

Uncontrolled physiological case-series study in humans.

PubMed 1948033 · doi:10.1126/science.1948033 · record verified 2026-08-27

What was done

Human subjects underwent a 68-hour fast during which net hepatic glycogen concentration was serially measured at 3- to 12-hour intervals using 13C nuclear magnetic resonance (NMR) spectroscopy. Whole-body glucose production was measured simultaneously using a tritiated glucose tracer. Net gluconeogenesis was calculated by subtracting the rate of net hepatic glycogenolysis from total whole-body glucose production.

What was found

Gluconeogenesis accounted for 64 +/- 5% (mean +/- standard error of the mean) of total glucose production during the first 22 hours of fasting. In the subsequent 14-hour and 18-hour periods of the fast, gluconeogenesis accounted for 82 +/- 5% and 96 +/- 1% of total glucose production, respectively.

Why it matters

This study demonstrates that gluconeogenesis provides the majority of endogenous glucose in humans even in the first 22 hours of fasting, challenging prior assumptions that glycogenolysis supplies the bulk of early fasting glucose.

Limits

The abstract does not disclose the sample size, demographics, or health status of the participants. Gluconeogenesis was determined indirectly by subtraction rather than through direct tracer incorporation.

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