Ketone infusion lowers hormonal responses to hypoglycaemia: evidence for acute cerebral utilization of a non-glucose fuel

Clin Sci (Lond). 1991 Aug;81(2):189-94. doi: 10.1042/cs0810189.


1. The effect of hyperketonaemia on counter-regulatory hormone responses to hypoglycaemia has been examined in six healthy subjects. 2. A controlled, step-wise reduction in blood glucose concentration was achieved by adjusting the rate of glucose infusion during a primed-continuous infusion of soluble insulin (1.5 m-units min-1 kg-1 body weight, plasma insulin concentration approximately 90 m-units/l). Simultaneous infusion of either saline or beta-hydroxybutyrate (3 mg min-1 kg-1 body weight) was administered in a single-blind fashion, in random order. Despite a need for 40% more glucose during the ketone infusion, an identical fall in blood glucose concentration was achieved in each study. 3. The glycaemic threshold for stimulating an adrenaline response of 0.41 nmol/l was reduced from 3.1 to 2.8 mmol/l (P less than 0.05) during ketone infusion, and that for stimulating a response of more than 50% of basal from 3.6 to 3.1 mmol/l (P less than 0.001). The peak adrenaline response fell from 7.97 to 2.6 nmol/l (P less than 0.04). Peak noradrenaline, cortisol and growth hormone responses were also significantly lower during ketone infusion (P = 0.04, 0.001 and 0.006, respectively). Glucagon responses alone were unaffected by hyperketonaemia. 4. The provision of an alternate metabolic fuel thus produced immediate changes in the neurohumoral responses to hypoglycaemia. This is consistent with the hypothesis that human nervous tissue can metabolize ketones acutely.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • 3-Hydroxybutyric Acid
  • Adult
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Brain / metabolism*
  • Epinephrine / blood
  • Female
  • Growth Hormone / blood
  • Humans
  • Hydrocortisone / blood
  • Hydroxybutyrates / blood*
  • Insulin / pharmacology*
  • Ketone Bodies / blood*
  • Male
  • Norepinephrine / blood
  • Single-Blind Method


  • Blood Glucose
  • Hydroxybutyrates
  • Insulin
  • Ketone Bodies
  • Growth Hormone
  • 3-Hydroxybutyric Acid
  • Hydrocortisone
  • Norepinephrine
  • Epinephrine