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

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 healthymenages 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 pulsatileACTHstrongly 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.