FP13-4 Dose-Dependent Inhibition Of Acyl- and Desacyl-Ghrelin Release In Healthy Young MEN During A Euglycemic Hyperinsulinemic Clamp. Possible Role Of Ghrelin In Growth Hormone (GH) Regulation

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP13-GI Peptides, Beta Cells & Glycemia
Translational
Saturday, June 15, 2013: 11:00 AM-11:30 AM
Presentation Start Time: 11:15 AM
Room 304 (Moscone Center)

Poster Board SAT-834
Ralf Manfred Nass*1, Jianhua Liu2, Suzan S Pezzoli2, Leon S Farhy2, James Patrie3, Bruce D Gaylinn2 and Michael O Thorner2
1Univ of Virginia Hlth System, Charlottesville, VA, 2University of Virginia Health System, Charlottesville, VA, 3University of Virginia, School of Medicine, Charlottesville, VA
Ghrelin is a 28-amino acid peptide with orexigenic and GH-releasing effects and it plays a role in energy homeostasis. Ghrelin is found in the circulation in two main forms: acyl- and desacyl-ghrelin. The orexigenic and GH-releasing effects of ghrelin are thought to be mediated by acyl-ghrelin. The aim of this study was to examine the dose-dependent characteristics of insulin inhibition of acyl- and desacyl-ghrelin and to test whether insulin-induced changes in ghrelin release are accompanied by changes in GH secretion.

Subjects and Methods: Eight men, age (mean ± SD)  21.9 ± 2.2 yr; BMI 24 ± 1.7kg/m2were studied in a single-blind, placebo-controlled study during two overnight admissions on the Clinical Research Unit. During a euglycemic hyperinsulinemic clamp, volunteers received on one admission a graded 5-h insulin infusion (mU/kg/min): 2 (0900-0910h); 1 (0910-1100h); 0.3 (1100-1230h); 0.1 (1230-1400h); and saline infusion (1400-1530h). On a separate admission volunteers received a 6.5-hr saline infusion. Plasma acyl- and desacyl-ghrelin (using an in-house two-site sandwich assay), GH, insulin and cortisol were measured every 10 min from 0700-1530h. Data were analyzed by way of linear mixed models with Bonferroni correction to compare the last hour of each infusion period.

Results:Under euglycemic conditions, there was a significant (p<0.01) difference in the mean within-subject change in acyl-ghrelin and desacyl-ghrelin (pg/ml) concentrations between interventions during the highest insulin infusion rate (1 mU/kg/min) (mean ± SE; admission: saline; insulin: acyl-ghrelin: 34.78 ± 1.86; 19.24  ± 1.07; desacyl-ghrelin: 38.33 ± 1.36; 23.45 ± 0.94). Desacyl- (but not acyl-) ghrelin levels continued to be suppressed (p<0.01) during the next insulin infusion rate of 0.3 mU/kg/min (mean ± SE;  admission: saline; insulin: 35.10 ± 1.32; 23.58 ± 0.97). The geometric mean within-subject ratio fold-change in GH levels (ng/ml) was significantly higher (p<0.05) when compared to the saline admission day during the 0.1 mU/kg/min infusion rate (mean ± SE; insulin; saline: 10.97 ± 1.12; 2.6 ± 0.5). Cortisol levels did not differ.

Conclusion: Insulin inhibits the release of acyl-and desacyl-ghrelin in healthy young men in a dose-dependent manner. The suppression of acyl-and desacyl-ghrelin has a rapid onset, but upon gradual withdrawal of insulin, the recovery of acyl-ghrelin is faster than that of desacyl-ghrelin. In addition, the recovery of ghrelin is followed by a significant increase in GH.

Disclosure: MOT: Founder, Ammonett Pharma, Recipient Award, Novo Nordisk, Advisory Group Member, Pfizer, Inc., Advisory Group Member, Ipsen, Advisory Group Member, Chaisma. Nothing to Disclose: RMN, JL, SSP, LSF, JP, BDG

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: 1R01DK076037 (to MOT)R01DK082805 (LSF)