Owen · The Journal of clinical investigation 1969 · Uncontrolled prospective metabolic cohort study · n=11

Liver and kidney metabolism during prolonged starvation.

Cited 873 times in the scientific literature.

Level 4 - case-series / case-control

Uncontrolled physiological case series in a small cohort without a control group.

PubMed 5773093 · doi:10.1172/JCI106016 · record verified 2026-08-30

What was done

Circulating concentrations of insulin, growth hormone, glucose, free fatty acids, glycerol, beta-hydroxybutyrate, acetoacetate, and alpha-amino nitrogen were measured in 11 obese subjects during prolonged starvation. In 5 of these subjects, the sites and estimated rates of gluconeogenesis and ketogenesis were quantified across the liver and kidneys after 5 to 6 weeks of fasting using organ substrate balances.

What was found

Blood glucose and insulin concentrations fell acutely during the first 3 days of fasting, and alpha-amino nitrogen fell after 17 days. Free fatty acids, beta-hydroxybutyrate, and acetoacetate did not reach a plateau until after 17 days. Estimated total glucose production at 5 to 6 weeks of starvation decreased to approximately 86 g/24 hr, with the liver contributing about one-half and the kidneys contributing the remainder. Nearly all lactate, pyruvate, glycerol, and amino acid carbons extracted by the liver and kidneys were converted to glucose.

Why it matters

This study established that the kidneys become an equal partner to the liver in endogenous gluconeogenesis during prolonged starvation.

Limits

The sample size was very small (n = 11 overall, n = 5 for renal and hepatic catheterization), restricted exclusively to obese subjects undergoing therapeutic fasting, and lacked a non-obese control group. The abstract does not report variance metrics or exact baseline vs final numerical concentrations for circulating hormones and substrates.

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