Ghrelin Secretory Dynamics and the Temporal Coupling with GH after Overnight Fasting, and in Response to Oral Glucose Intake in Healthy Men

Presentation Number: OR14-2
Date of Presentation: April 3rd, 2017

Ali Iranmanesh*1, Donna Marie Lawson2, Casey Whipple3 and Johannes Veldhuis4
1VA Medical Center, Salem, VA, 2Veteran Affairs Medical Center, Salem, VA, 3Virginia Tech Carilion School of Medicine, Roanoke, VA, 4Endocrine Research Unit, Mayo Graduate Medical Education, Mayo Center for Translational Sciences, Rochester, MN


Context: Higher circulating ghrelin concentrations after an overnight fast and the respective decrease after food intake correspond closely with GH fluctuations under similar settings, except that post-prandial rebound reported for GH has not been fully defined for ghrelin.

Design: In this study, circulating ghrelin and GH concentrations in 20 healthy men (age: 18-60 yrs, BMI: 18-39 Kg/m2) were assessed after an overnight fast on 2 randomly assigned occasions, either after oral ingestion of 75 g dextrose solution or equal volume of water. Sessions were 6.5 h long, starting between 0800-0900 hrs. Blood was collected at 10-min intervals for ghrelin and GH measurements. Regression, cross-correlation, deconvolution, ApEn, and cross-ApEn procedures were utilized for data analysis.

Results: In contrast to water day, decreases in circulating ghrelin concentrations after dextrose intake were followed by a peak corresponding to the GH rebound. Nutrient-induced changes in ghrelin level maintained a positive correlation with GH (r2/P: 0.52/<0.0001). The rebound in ghrelin concentration was significantly cross-correlated with GH over the period from 120-210 min (post-dextrose), with maximal correlation depicted at 160 min (r2/P: 0.40/<0.001). Deconvolution analysis identified basal and pulsatile secretory events contributing to total ghrelin secretion (ng/mL/6.5h), both on water and dextrose days, with significant decreases in basal (7.6 ± 2.4 v 10.7 ± 3.4: P=0.0001), but marked increases in pulsatile (3.1 ± 1.7 v 1.5 ± 1.0: P=0.00001) ghrelin release after dextrose intake. The latter was attributed to increased mass of ghrelin secreted per burst (581 ± 190 v 278 ± 146 pg/mL: P<0.000001). ApEn and cross-ApEn respectively revealed for dextrose intake to improve: (1) orderliness of ghrelin secretory events (0.35 ± 0.13 v 0.65 ± 0.20: P=<0.00001); and (2) ghrelin/GH (feedforward, 0.58 ± 0.15 v 0.85±0.26: P=0.00008) and GH/ghrelin (feedback, 0.40±0.08 v 0.51±0.16: P=0.0079) synchrony.

Conclusion: The results of this study disclose glucose-induced rebound in ghrelin release, and its temporal coupling with GH. This finding along with close correlation between circulating ghrelin and GH concentrations at r2 value of 0.52 could imply a major role of nutrient-induced ghrelin modulation in daily GH production. The latter hypothesis is further supported by the observation of improved ghrelin/GH feedforward and feedback mechanisms, after glucose ingestion.


Nothing to Disclose: AI, DML, CW, JV