Supplementary Materials Supplemental Data supp_96_9_2882__index. secretion. Glucose direct exposure selectively augmented the mass of ACTH ( 0.001) and of cortisol (= 0.004) secreted per burst without altering burst number or basal secretion. The increment in pulsatile ACTH strongly predicted the increment in pulsatile cortisol ( 10?4; R2 = 0.325) secretion. Abdominal visceral excess fat positively forecast the glucose-induced increment in cortisol secretory-burst mass (= 0.019). According to approximate entropy analysis, glucose input also enhanced the joint synchrony of ACTH-cortisol secretory patterns ( 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 Nalfurafine hydrochloride distributor glucocorticoid secretion in healthy men. Visceral adiposity is usually a predictor of the glucose-stimulated increment in burst-like cortisol output, suggesting an additional possible mechanism for increased cardiovascular risk in abdominal obesity. Ingestion of glucose, amino acids, protein, or mixed meals tends to increase serum and salivary cortisol concentrations in healthy adults (1C8). Gender, time of day, and enteric peptides, such as glucagon-like peptide, tachykinins, and glucose-dependent insulinotropic peptide, may modulate such effects (7C10). In pathological states like ACTH-independent macronodular adrenal hyperplasia, anomalous or exaggerated expression of peptidyl and adrenergic receptors may contribute to excessive cortisol secretion with meals (11, 12). However, the precise mechanisms that mediate oral nutrient effects in healthy individuals are not known. Indeed, under physiological conditions, both ACTH-dependent and ACTH-independent mechanisms of food-induced cortisol secretions have been postulated (3, 13C15). To our knowledge, pulsatile ACTH secretion after caloric ingestion has never been quantified adequately by current standards (16). This limitation is usually significant because pivotal meal-triggered mechanisms could include amplification of basal (nonpulsatile) or pulsatile ACTH secretion, enhancement of ACTH-cortisol synchrony, potentiation of ACTH-cortisol dose-responsiveness, and augmentation of adrenal cortisol secretion independently of ACTH. The present investigations used a paired within-subject crossover design with frequent (10-min) sampling over 6.5 h to measure time-varying ACTH and cortisol concentrations in 58 adults before and after Nalfurafine hydrochloride distributor ingestion of a fixed glucose load or equivalent volume of water. Deconvolution, approximate entropy (ApEn), and ACTH-cortisol dose-response analyses were then applied to test the foregoing hypotheses noninvasively. Topics and Methods Topics Fifty-eight healthy guys had been recruited to participate after offering voluntary written Felypressin Acetate educated consent accepted by the neighborhood Institutional Review Plank. The admissible a long time was 19C78 yr, with body mass index of 20C39 kg/m2. Exclusion diagnoses were congestive cardiovascular failure, severe or chronic liver or renal disease, anemia, hypothalamopituitary disease, neuropsychiatric drug direct exposure, glucocorticoid make use of, systemic inflammatory disease, malignancy, drug abuse, intracranial disease, anti snoring, and diabetes mellitus. Inclusion requirements Nalfurafine hydrochloride distributor were community-dwelling, individually living, consenting adults with steady diurnal work behaviors, bodyweight (within 2 kg in three months), and leisure exercise patterns. Process Subjects (n = 58) undertook two 10-min sampling periods after over night fasting, starting at 0800 h. At 0830 h, glucose (75 g) or the same level of water (10 ounces) was administered orally. Bloodstream sampling continuing thereafter for 6 more time (until 1430 h). Plasma was attained in chilled tubes that contains divalent-steel chelators. An stomach Nalfurafine hydrochloride distributor computed tomography (CT) scan was performed at the L3C4 interspace to estimate stomach visceral excess fat (AVF) cross-sectional area, as described (17). In three subjects, there was a delay (not exceeding 1 h) in starting the protocol. Assays Circulating concentrations of ACTH, cortisol, and insulin were assayed by Immulite 2000 (Siemens Healthcare Diagnostics, Flanders, NJ), using reagents from the Siemens Healthcare Diagnostics. The assay for cortisol has a detection range of 0.2C50 g/dl with intra-and interassay coefficients.