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 exaggerat ed GH responses to several stimuli, including GHRH, have been describe d. GH-releasing peptide-6 (GHRP-6) is a synthetic hexapeptide that spe cifically 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 combinat ion with GHRH on GH secretion in DM 1. Six type 1 diabetic males and s ix age-, sex-, and body mass index-matched control volunteers were stu died. Each subject received GHRH (100 mu g iv), GHRP-6 (90 mu g iv), a nd 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 us. 19.3 +/- 6.0 mu g/L; P = 0.016), GHRP-6 (66.2 +/- 9.6 us. 39.9 +/ - 6.3 mu g/L; P = 0.05), and GHRH plus GHRP-6 (81.8 +/- 4.4 vs. 53.7 /- 8.2 mu g/L; P = 0.01). An additive GH response to combined administ ration of these two peptides was observed in diabetic patients. Serum insulin-like growth factor (IGF)-1 levels were diminished in DM 1, wit h respect to normal subjects (145.2 +/- 21.5 vs. 269.7 +/- 42.0 mu g/L ; P = 0.01), whereas IGF-binding protein-3 levels were not significant ly different between DM-1 and controls. In summary, GHRP-6 is a potent stimulus for GH secretion in DM 1. The combined administration of GHR P-6 plus GHRH constitutes the most powerful stimulus for GH secretion in DM 1. These patients exhibit a greater GH secretory capacity than n ormal subjects, probably caused by a diminished tone in the IGF-1 sust ained negative feedback control exerted upon somatotroph responsivenes s.