Circulating levels of incretin hormones and amylin in the fasting state and after oral glucose in GH-deficient patients before and after GH replacement: a placebo-controlled study.
OBJECTIVE
Hyperinsulinemia in association with GH excess is considered a compensatory response to insulin resistance, but the possibility of alternative insulinotropic mechanisms has not been investigated in vivo. It is also unknown how GH influences the secretion from pancreatic beta-cells of amylin, a peptide which regulates prandial glucose homeostasis and may be linked to development of beta-cell dysfunction. We therefore measured plasma concentrations of two gut insulinotropic hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulin-releasing peptide (GIP), and total as well as non-glycosylated amylin, in 24 GH-deficient adults before and after 4 months of GH replacement (daily evening injections of 2 IU GH/m).


METHODS
Double-blind, placebo-controlled, parallel study.


METHODS
All participants underwent an oral glucose tolerance test (OGTT) at 0 and 4 months.


RESULTS
A 33% suppression of fasting GLP-1 concentrations was measured in the GH group at 4 months (P=0.02), whereas a non-significant increase occurred in the placebo group (P=0.08). Fasting levels of GIP and amylin did not change significantly after 4 months in either group. The incremental response in GLP-1 during the OGTT was significantly lower after GH treatment as compared with both baseline (P=0.02) and the response in the placebo group (P=0. 03). The stimulation of GIP secretion following OGTT was similar on all occasions. The OGTT-induced incremental response in non-glycosylated amylin was moderately elevated after GH treatment as compared with placebo (P=0.05). Plasma concentrations of glucose and insulin, both in the fasting state and after the OGTT, were higher after GH treatment, but the ratio between amylin and insulin remained unchanged.


CONCLUSIONS
GH-induced hyperinsulinemia is accompanied by proportionate elevations in amylin concentrations and a blunting of gut GLP-1 secretion. The mechanisms underlying the suppression of GLP-1 remain to be elucidated.
Jørgensen
J O
JO
Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Aarhus, Denmark. jolj@dadlnet.dk
Rosenfalck
A M
AM
Fisker
S
S
Nyholm
B
B
Fineman
M S
MS
Schmitz
O
O
Madsbad
S
S
Holst
J J
JJ
Christiansen
J S
JS
D000328:Adult; D000682:Amyloid / Q000097:blood*; D005215:Fasting; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005768:Gastrointestinal Hormones / Q000097:blood*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D058228:Islet Amyloid Polypeptide; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D011498:Protein Precursors / Q000097:blood
D000682:Amyloid; D005768:Gastrointestinal Hormones; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; D011498:Protein Precursors; C055453:glucagon-like peptide 1 (7-36)amide; D019382:Human Growth Hormone; D005749:Gastric Inhibitory Polypeptide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D013006:Growth Hormone; D005934:Glucagon; D005947:Glucose