title: Growth hormone (GH) response to GH-releasing peptide-6 in patients with insulin-dependent diabetes mellitus.
abstract: In insulin-dependent diabetes mellitus (IDDM), inappropriate growth hormone (GH) responses to several stimuli, including GH-releasing hormone (GHRH), have been described. A decreased hypothalamic somatostatinergic tone is one of the most likely explanations for these findings. His-DTrp-Ala-Trp-DPhe-Lys-NH2 [GH-releasing peptide-6 [GHRP-6]] is a synthetic hexapeptide that stimulates GH release in vitro and in vivo. The mechanism of action of GHRP-6 is unknown, but it probably does not inhibit hypothalamic somatostatin secretion. Also, GHRH and GHRP-6 apparently activate different intracellular pathways to release GH. The aim of this study was to evaluate whether there is a differential effect of IDDM on GHRP-6- and GHRH-induced GH secretion. Six patients with IDDM and seven control subjects were studied. Each subject received GHRP-6 (1 microgram/kg intravenously [IV]), GHRH (100 micrograms IV), and GHRP-6 + GHRH on 3 separate days. GH peak values (mean +/- SE in micrograms per liter) were similar in controls and diabetics after GHRH (22.5 +/- 7.8 v 24.0 +/- 9.7) and after GHRP-5 (20.5 +/- 5.3 v 24.4 +/- 6.3). The association of GHRP-6 and GHRH induced a significantly higher GH release than administration of the isolated peptides in both groups. The synergistic GH response to combined administration of GHRP-6 and GHRH was not different in controls (70.5 +/- 20.0) and diabetics (119.0 +/- 22.2). In summary, the effectiveness of GHRP-6 in IDDM could reinforce the evidence that this peptide probably does not release GH through a decrease in hypothalamic somatostatin secretion. Moreover, our data suggest that both GHRH and GHRP-6 releasing mechanisms are unaltered in IDDM.
authors.affiliation: Division of Endocrinology, Universidade Federal de São Paulo, Escola Paulista de Medicina, Brazil.
authors.forename: R F
authors.initials: RF
authors.lastname: Villas-Boas Weffort
authors.forename: J C
authors.initials: JC
authors.lastname: Ramos-Dias
authors.forename: C
authors.initials: C
authors.lastname: Chipoch
authors.forename: A M
authors.initials: AM
authors.lastname: Lengyel
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D012016:Reference Values
chemical_list: D006728:Hormones; D009842:Oligopeptides; D019382:Human Growth Hormone; C041048:growth hormone releasing hexapeptide; D013007:Growth Hormone-Releasing Hormone