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-NH 2 (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 μg/kg intravenously [IV]), GHRH (100 μg 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-6 (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.