J. Endocrinol. Invest. 24: RC19-RC21, 2001
RAPID COMMUNICATION
Post-prandial decrease of circulating human ghrelin levels
M. Tschöp, R. Wawarta, R.L. Riepl, S. Friedrich, M. Bidlingmaier, R. Landgraf, and C. Folwaczny
Medizinische Klinik Innenstadt, Ludwig-Maximilians Universität, Munich, Germany
ABSTRACT. Ghrelin, an endogenous ligand of the GH secretagogue-receptor, has recently been
shown to stimulate GH secretion and to have orexigenic and adipogenic effects in rodents, but little
is known about its regulation and biological function in humans. Gastric motor function is under con-
trol of the central nervous system; however, the afferent and efferent loops of this feedback control
mechanism remain to be elucidated. In the study presented here we investigated the effect of nutri-
ent intake on circulating human ghrelin levels, and a possible association between ghrelin levels and
gastric emptying. Ten healthy volunteers received a standard meal after an overnight fast. Food intake
significantly decreased plasma ghrelin levels from 248.5 15.0 to 179.5 17.9 fmol/ml (120 min after
meal, p=0.047). Gastric emptying half-time (non-invasive 13C-octanoic acid breath test) was corre-
lated with fasting plasma ghrelin levels (r=0.74, p=0.0013). Ghrelin appears to be one possible candi-
date to provide feedback signaling between nutrient intake, gastric motor function and the central ner-
vous system.
(J. Endocrinol. Invest. 24: RC19-RC21, 2001)
©2001, Editrice Kurtis
INTRODUCTION
METHODS
Gastric motor function is under the control of the central
nervous system; however, the afferent and efferent loops of
this feedback control mechanism remain to be elucidated.
Ghrelin, an endogenous ligand of the GH secretagogue re-
ceptor (GHS-R), stimulates GH release from the pituitary
in vitro and in vivo. GHS-Rs are also present in hypothalam-
ic areas of feeding control, the pancreas, intestine and in
adipocytes (1, 2). Recent studies in rodents show a role of
ghrelin as an afferent signal to the hypothalamus indicating
the need for increased metabolic efficiency (3). Hence,
ghrelin might represent a missing endocrine link between
stomach, hypothalamus and pituitary.
Ten healthy volunteers (5 men, 5 women, BMI 22.2 1.0
kg/m2, age 28.9 3.2 yr) received a standardized solid meal la-
beled with 13C2-octanoic acid (483 kcal, 16 g fat, 65 g carbo-
hydrate, 18 g protein) after an overnight fast. Plasma samples
were collected before and at various intervals following the
meal (30, 60, 120 and 240 min) in a stress-free environment
between 8:00 and 12:00 h. The present study was approved
by the Ethics Committee of the Ludwig Maximilians Uni-
versity, Munich, and all volunteers gave informed consent pri-
or to the start of the study. Human plasma ghrelin was mea-
sured with a commercial RIA (Phoenix Pharmaceuticals, Inc.,
Belmont, CA) that uses 125I-labeled bioactive ghrelin as a trac-
er molecule and a polyclonal antibody raised in rabbits
against full length, octanoylated human ghrelin. No cross-
reactivity was found with human secretin, vasoactive intesti-
nal peptide, prolactin releasing peptide-31, galanin, GH re-
leasing hormone, neuropeptide Y or other relevant molecules.
The inter-assay CV is 9.0-13.6% (no.=10), the intra-assay CV
is 4.5-5.3% and the assay sensitivity is 5.4 pg/tube (ED-80).
Plasma insulin and glucose levels were measured by RIA and
the glucose oxidase method. All data are presented as
mean SE. Statistical analysis was performed using one-way
ANOVA with Fisher’s LSD post hoc testing and linear regres-
sion analysis was performed using Sigmastat Software.
To further clarify the physiological role of ghrelin in the
regulation of energy balance and gastric motor function we
investigated the influence of nutrient intake on circulating
ghrelin levels.
Key-words: Gastric emptying, ghrelin.
Correspondence: Dr. Christian Folwaczny, Medizinische Klinik, Klinikum
Innenstadt der Ludwig-Maximilians Universität, Ziemssenstr. 1, 80336 Munich,
Germany.
RESULTS
Food intake significantly increased plasma glucose levels from
75.6 2.7 to 97.0 4.9 mg/dl (30 min after meal, p=0.004) (Fig.
1A). Insulin levels increased from 11.2 2.6 to 64.5 7.1 ng/ml
Accepted February 21, 2001.
RC19