Ghrelin secretion is inhibited by glucose load and insulin-induced hypoglycaemia but unaffected by glucagon and arginine in humans.
OBJECTIVE
Circulating ghrelin levels are increased by fasting and decreased by feeding, glucose load, insulin and somatostatin. Whether hyperglycaemia and insulin directly inhibit ghrelin secretion still remains matter of debate. The aim of the present study was therefore to investigate further the regulatory effects of glucose and insulin on ghrelin secretion.


METHODS
We studied the effects of glucose [oral glucose tolerance test (OGTT) 100 g orally], insulin-induced hypoglycaemia [ITT, 0.1 IU/kg insulin intravenously (i.v.)], glucagon (1 mg i.v.), arginine (0.5 mg/kg i.v.) and saline on ghrelin, GH, insulin, glucose and glucagon levels in six normal subjects.


METHODS
In all the sessions, blood samples were collected every 15 min from 0 up to + 120 min. Ghrelin, GH, insulin, glucagon and glucose levels were assayed at each time point.


RESULTS
OGTT increased (P < 0.01) glucose and insulin while decreasing (P < 0.01) GH and ghrelin levels. ITT increased (P < 0.01) GH but decreased (P < 0.01) ghrelin levels. Glucagon increased (P < 0.01) glucose and insulin without modifying GH and ghrelin. Arginine increased (P < 0.01) GH, insulin, glucagon and glucose (P < 0.05) but did not affect ghrelin secretion.


CONCLUSIONS
Ghrelin secretion in humans is inhibited by OGTT-induced hyperglycaemia and ITT but not by glucagon and arginine, two substances able to increase insulin and glucose levels. These findings question the assumption that glucose and insulin directly regulate ghrelin secretion. On the other hand, ghrelin secretion is not associated with the GH response to ITT or arginine, indicating that the somatotroph response to these stimuli is unlikely to be mediated by ghrelin.
Division of Endocrinology, Department of Internal Medicine, Erasmus University of Rotterdam, the Netherlands.
Fabio
F
Broglio
Cristina
C
Gottero
Flavia
F
Prodam
Silvia
S
Destefanis
Carlotta
C
Gauna
Elisa
E
Me
Fabrizio
F
Riganti
Daniela
D
Vivenza
Anna
A
Rapa
Valentino
V
Martina
Emanuela
E
Arvat
Gianni
G
Bona
Aart Jan
AJ
van der Lely
Ezio
E
Ghigo
D000328:Adult; D001120:Arginine; D054439:Ghrelin; D005934:Glucagon; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008297:Male; D036361:Peptide Hormones / Q000097:blood / Q000378:metabolism*; D012636:Secretory Rate / Q000187:drug effects
D054439:Ghrelin; D007328:Insulin; D036361:Peptide Hormones; D013006:Growth Hormone; D005934:Glucagon; D001120:Arginine; D005947:Glucose