Metabolic and endocrine effects of physiological increments in plasma ghrelin concentrations.
BACKGROUND
Growing evidence indicates that the administration of large amounts of ghrelin to humans increases circulating concentrations of several pituitary and adrenal hormones, induces hyperglycemia and reduces serum insulin concentrations. At present, it is not known whether physiological increments in plasma ghrelin concentrations affect glucose kinetics or hormone concentrations in humans.


RESULTS
We compared the effects of two- and three-fold increments in plasma ghrelin concentrations in eight healthy subjects during a 2 h intravenous infusion of 7.5 (GHRE7.5), 15 (GHRE15) pmol kg(-1) min(-1) acylated human ghrelin or placebo (PL), in a randomized double-blind study. Compared with PL (146 +/- 24 pM) plasma ghrelin concentrations increased at 120 min (p<0.001) about two-fold after GHRE7.5 (300 +/- 35 pM) and three-fold after GHRE15 (494 +/- 30 pM). GHRE15 significantly increased circulating concentrations of NEFA, GH, ACTH, epinephrine, and prolactin (p<0.01). GHRELIN7.5 significantly (p<0.01) increased only serum GH concentrations. Neither ghrelin infusions changed glucose flux or circulating concentrations of glucose, insulin, C-peptide, glucagon, IGF-1, cortisol and norepinephrine.


CONCLUSIONS
GH secretion is the only response that is stimulated by physiological increments in plasma ghrelin concentrations; about three-fold increases in plasma ghrelin concentrations are required to elicit the responses of epinephrine, prolactin, ACTH and NEFA.
Lucidi
Paola
P
Department of Internal Medicine, Section of Internal Medicine and Endocrine and Metabolic Sciences (I.M.I.S.E.M.), University of Perugia, Via Enrico Dal Pozzo, 06126 Perugia, Italy.
Murdolo
Giuseppe
G
Di Loreto
Chiara
C
Parlanti
Natascia
N
De Cicco
Arianna
A
Fatone
Cristina
C
Taglioni
Chiara
C
Fanelli
Carmine
C
Broglio
Fabio
F
Ghigo
Ezio
E
Bolli
Geremia B
GB
Santeusanio
Fausto
F
De Feo
Pierpaolo
P
D000215:Acylation; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004703:Endocrine System / Q000187:drug effects*; D004837:Epinephrine / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D054439:Ghrelin; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000008:administration & dosage* / Q000097:blood* / Q000502:physiology; D011388:Prolactin / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D007328:Insulin; D036361:Peptide Hormones; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013006:Growth Hormone; D004837:Epinephrine