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This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/E1829    most recent 00682.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Vestergaard, E. T. Articles by Jorgensen, J. O. L. Search for Related Content PubMed PubMed Citation Articles by Vestergaard, E. T. Articles by Jorgensen, J. O. L.

Constant intravenous ghrelin infusion in healthy young men: clinical pharmacokinetics and metabolic effects

¹Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital; and ²Department of Pharmacology, University of Aarhus, Aarhus, Denmark

Submitted 13 December 2006 ; accepted in final form 31 January 2007

Ghrelin levels fluctuate rapidly and dynamically with surges before meal times and postprandial troughs, and ghrelin increases appetite and food intake. Circulating ghrelin correlates negatively with body mass index (BMI), but obese individuals have a reduced postprandial decrease in ghrelin levels. Whether this reflects changes in secretion or clearance of ghrelin is uncertain. We therefore studied the pharmacokinetics of ghrelin in relation to anthropometric and biochemical measures. We also studied the effects of ghrelin on hormones and metabolites. In fasting humans, we used a constant infusion rate of ghrelin lasting 180 min at 5 pmol·kg body wt^–1·min^–1 in a randomized, double-blind, placebo-controlled crossover study. Serum ghrelin (s-ghrelin; total levels) was distributed and eliminated according to a two-compartment model. s-Ghrelin initial half-life was 24 ± 2 min and terminal half-life 146 ± 36 min, respectively. Mean residence time (MRT) of ghrelin was 93 ± 16 min. MRT correlated positively with both BMI (r = 0.51, P < 0.001) and high-density cholesterol (HDL) levels (r = 0.75, P < 0.001). Serum insulin levels remained constant during ghrelin infusion, whereas plasma glucose increased 0.3 ± 0.1 mmol/l (P < 0.01) and free fatty acid levels more than doubled (to 1.03 ± 0.08 mmol/l, P < 0.001), translating into a significant reduction of insulin sensitivity (P < 0.001). In conclusion, 1) we describe novel pharmacokinetics of ghrelin that are useful when tailoring ghrelin infusion rates in clinical experiments, 2) BMI and HDL correlate positively with MRT of infused ghrelin, and 3) supraphysiological ghrelin levels impair insulin sensitivity.

mean residence time; insulin sensitivity

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