GROWTH-HORMONE (GH) RESPONSE TO GH-RELEASING PEPTIDE-6 IN PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS

In insulin-dependent diabetes mellitus (IDDM), inappropriate growth ho rmone (GH) responses to several stimuli, including GH-releasing hormon e (GHRH), have been described, A decreased hypothalamic somatostatiner gic tone is one of the most likely explanations for these findings. Hi s-DTrp-Ala-Trp-DPhe-Lys-NH2 (GH-releasing peptide-6 [GHRP-6]) is a syn thetic hexapeptide that stimulates GH release in vitro and in vivo, Th e mechanism of action of GHRP-6 is unknown, but it probably does not i nhibit hypothalamic somatostatin secretion. Also, GHRH and GHRP-6 appa rently activate different intracellular pathways to release GH, The ai m 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 I DDM and seven control subjects were studied. Each subject received GHR P-6 (1 mu g/kg intravenously [IV]), GHRH (100 mu g IV), and GHRP-6 + G HRH 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 a ssociation of GHRP-6 and GHRH induced a significantly higher GH releas e than administration of the isolated peptides in both groups. The syn ergistic 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 t he evidence that this peptide probably does not release GH through a d ecrease in hypothalamic somatostatin secretion, Moreover, our data sug gest that both GHRH and GHRP-6 releasing mechanisms are unaltered in I DDM. Copyright (C) 1997 by W.B. Saunders Company.