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Esben Thyssen Vestergaard

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

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Constant intravenous ghrelin infusion in healthy young men : Clinical pharmacokinetics and metabolic effects. / Vestergaard, Esben Thyssen; Hansen, Troels Krarup; Gormsen, Lars Christian; Jakobsen, Preben; Moller, Niels; Christiansen, Jens Sandahl; Jorgensen, Jens Otto Lunde.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 292, No. 6, 01.06.2007.

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@article{9aab3dbb0f7e4ca5b8388c53fac72867,
title = "Constant intravenous ghrelin infusion in healthy young men: Clinical pharmacokinetics and metabolic effects",
abstract = "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.",
keywords = "Insulin sensitivity, Mean residence time",
author = "Vestergaard, {Esben Thyssen} and Hansen, {Troels Krarup} and Gormsen, {Lars Christian} and Preben Jakobsen and Niels Moller and Christiansen, {Jens Sandahl} and Jorgensen, {Jens Otto Lunde}",
year = "2007",
month = jun,
day = "1",
doi = "10.1152/ajpendo.00682.2006",
language = "English",
volume = "292",
journal = "A J P: Endocrinology and Metabolism (Online)",
issn = "1522-1555",
publisher = "AMER PHYSIOLOGICAL SOC",
number = "6",

}

RIS

TY - JOUR

T1 - Constant intravenous ghrelin infusion in healthy young men

T2 - Clinical pharmacokinetics and metabolic effects

AU - Vestergaard, Esben Thyssen

AU - Hansen, Troels Krarup

AU - Gormsen, Lars Christian

AU - Jakobsen, Preben

AU - Moller, Niels

AU - Christiansen, Jens Sandahl

AU - Jorgensen, Jens Otto Lunde

PY - 2007/6/1

Y1 - 2007/6/1

N2 - 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.

AB - 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.

KW - Insulin sensitivity

KW - Mean residence time

UR - http://www.scopus.com/inward/record.url?scp=34447545671&partnerID=8YFLogxK

U2 - 10.1152/ajpendo.00682.2006

DO - 10.1152/ajpendo.00682.2006

M3 - Journal article

C2 - 17311892

AN - SCOPUS:34447545671

VL - 292

JO - A J P: Endocrinology and Metabolism (Online)

JF - A J P: Endocrinology and Metabolism (Online)

SN - 1522-1555

IS - 6

ER -