Growth hormone (GH) response to GH-releasing peptide-6 in type 1 diabetic patients with exaggerated GH-releasing hormone-stimulated GH secretion.
In type 1 diabetes mellitus (DM 1), high GH basal levels and exaggerated GH responses to several stimuli, including GHRH, have been described. GH-releasing peptide-6 (GHRP-6) is a synthetic hexapeptide that specifically stimulates GH release, both in vitro and in vivo. The aim of this study was to evaluate the effects of GHRP-6 alone or in combination with GHRH on GH secretion in DM 1. Six type 1 diabetic males and six age-, sex-, and body mass index-matched control volunteers were studied. Each subject received GHRH (100 microg iv), GHRP-6 (90 microg iv), and GHRH plus GHRP-6 on three separate days. GH peak values were higher in DM 1 patients than in control volunteers, after GHRH (52.2+/-9.8 vs. 19.3+/-6.0 microg/L; P = 0.016), GHRP-6 (66.2+/-9.6 vs. 39.9+/-6.3 microg/L; P = 0.05), and GHRH plus GHRP-6 (81.8+/-4.4 vs. 53.7+/-8.2 microg/L; P = 0.01). An additive GH response to combined administration of these two peptides was observed in diabetic patients. Serum insulin-like growth factor (IGF)-1 levels were diminished in DM 1, with respect to normal subjects (145.2+/-21.5 vs. 269.7+/-42.0 microg/L; P = 0.01), whereas IGF-binding protein-3 levels were not significantly different between DM-1 and controls. In summary, GHRP-6 is a potent stimulus for GH secretion in DM 1. The combined administration of GHRP-6 plus GHRH constitutes the most powerful stimulus for GH secretion in DM 1. These patients exhibit a greater GH secretory capacity than normal subjects, probably caused by a diminished tone in the IGF-1 sustained negative feedback control exerted upon somatotroph responsiveness.
Department of Endocrinology, Montecelo Hospital, Pontevedra, Spain.
P F
PF
Catalina
F
F
Mallo
M A
MA
Andrade
R V
RV
García-Mayor
C
C
Diéguez
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D012016:Reference Values
D004338:Drug Combinations; D009842:Oligopeptides; D019382:Human Growth Hormone; C041048:growth hormone releasing hexapeptide; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone