Ghrelin is suppressed by glucagon and does not mediate glucagon-related growth hormone release.
BACKGROUND
Glucagon stimulation is routinely used as a provocative test to assess growth hormone (GH) sufficiency in pediatrics. Ghrelin also markedly stimulates GH secretion. Because glucagon stimulates the promoter of the ghrelin gene in vitro as well as ghrelin secretion by the perfused rat stomach, we sought to determine whether ghrelin mediates glucagon-induced GH secretion.


METHODS
We compared ghrelin, GH, insulin and glucose responses following administration of 0.03 mg/kg intravenously (iv; max. 1 mg) and 0.1 mg/kg intramuscularly (im; max. 2 mg) of glucagon in two groups (n = 10-11/group) of GH-sufficient children. We also measured ghrelin before and 6 min after iv administration of 1 mg glucagon in 21 adult subjects.


RESULTS
In children, glucagon caused a 26% decrease in ghrelin and a 72% increase in glucose concentrations that were independent of the dose or administration route of glucagon. In contrast, the insulin response was 2-3 times higher following administration of 0.1 mg/kg im compared to 0.03 mg/kg of glucagon iv. There was a significant correlation between the maximum decrease in ghrelin and increases in glucose (p = 0.03) but not in insulin. There was a significant correlation between ghrelin and GH area under the curve after controlling for the dose of glucagon (p = 0.03) but not for the maximum increase in glucose.In normal adults, glucagon administration caused a 7% decrease in ghrelin concentrations after 6 min (p = 0.0002).


CONCLUSIONS
Ghrelin does not play a causal role in the GH response to pharmacological glucagon administration, which suppresses ghrelin levels starting a few minutes after injection.
Hirsh
Denton
D
Endocrinology and Diabetes Unit, British Columbia's Children's Hospital, University of British Columbia, Vancouver, Canada.
Heinrichs
Claudine
C
Leenders
Bert
B
Wong
Alfred C K
AC
Cummings
David E
DE
Chanoine
Jean-Pierre
JP
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001786:Blood Glucose; D002648:Child; D002675:Child, Preschool; D005260:Female; D054439:Ghrelin; D005934:Glucagon / Q000008:administration & dosage*; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood; D008297:Male; D036361:Peptide Hormones / Q000097:blood*; D011446:Prospective Studies
D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D036361:Peptide Hormones; D019382:Human Growth Hormone; D005934:Glucagon