Glucose ingestion selectively amplifies ACTH and cortisol secretory-burst mass and enhances their joint synchrony in healthy men

J Clin Endocrinol Metab. 2011 Sep;96(9):2882-8. doi: 10.1210/jc.2011-0682. Epub 2011 Jul 13.


Context: Glucose intake is associated with a variable increase in adrenal glucocorticoid secretion.

Hypothesis: Glucose ingestion elevates cortisol secretion by 1) augmenting pulsatile ACTH release; and/or 2) enhancing ACTH-cortisol synchrony or dose-responsiveness.

Subjects: Fifty-eight healthy men ages 19-78 yr with computed tomography-estimated abdominal visceral fat participated in the study.

Location: The study was conducted at the Clinical Translational-Research Center and Veterans Affairs Medical Center.

Methods: We conducted frequent sampling of plasma ACTH and cortisol concentrations after glucose vs. water ingestion in the fasting state, as well as deconvolution, approximate entropy, linear-regression, and dose-response analysis.

Outcomes: After water ingestion, age was a negative correlate of the mass of ACTH (P = 0.009; R(2) = 0.119) and of cortisol (P < 0.001; R(2) = 0.269) secreted per burst. Glucose ingestion abolished both relationships but amplified pulsatile ACTH (P = 0.009) and cortisol (P = 0.001) secretion. Glucose exposure selectively augmented the mass of ACTH (P < 0.001) and of cortisol (P = 0.004) secreted per burst without altering burst number or basal secretion. The increment in pulsatile ACTH strongly predicted the increment in pulsatile cortisol (P < 10(-4); R(2) = 0.325) secretion. Abdominal visceral fat positively forecast the glucose-induced increment in cortisol secretory-burst mass (P = 0.019). According to approximate entropy analysis, glucose input also enhanced the joint synchrony of ACTH-cortisol secretory patterns (P ≤ 0.001). Caloric intake did not affect analytical dose-response estimates of ACTH potency and efficacy or adrenal sensitivity.

Conclusion: Conjoint augmentation of the mass of ACTH and cortisol secreted per burst and enhancement of ACTH-cortisol synchrony underlie glucose-induced glucocorticoid secretion in healthy men. Visceral adiposity is a predictor of the glucose-stimulated increment in burst-like cortisol output, suggesting an additional possible mechanism for increased cardiovascular risk in abdominal obesity.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adrenocorticotropic Hormone / blood
  • Adrenocorticotropic Hormone / metabolism*
  • Adult
  • Aged
  • Glucose / administration & dosage*
  • Humans
  • Hydrocortisone / blood
  • Hydrocortisone / metabolism*
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / physiology
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / drug effects*
  • Pituitary-Adrenal System / physiology


  • Adrenocorticotropic Hormone
  • Glucose
  • Hydrocortisone