EVIDENCE FOR AN INHIBITORY EFFECT OF PHYSIOLOGCAL LEVELS OF INSULIN ON THE GROWTH-HORMONE (GH) RESPONSE TO GH-RELEASING HORMONE IN HEALTHY-SUBJECTS

It has been previously reported that in healthy subjects, the acute re duction of free fatty acids (FFA) levels by acipimox enhances the GH r esponse to GHRH. In the present study, the GH response to GHRH was eva luated during acute blockade of lipolysis obtained either by acipimox or by insulin at different infusion rates. Six healthy subjects (four men and two women, 25.8 +/- 1.9 yrs old, mean +/- SE) underwent three GHRH tests (50 mu g iv, at 1300 h) during: 1) iv 0.9% NaCl infusion (1 200-1500 h) after oral acipimox administration (250 mg) at 0700 h and at 1100 h; 2) 0.1 mU.kg(-l).min(-l) euglycemic insulin clamp (1200-150 0 h) after oral acipimox administration (250 mg at 0700 h and at 1100 h); 3) 0.4 mU.kg(-l).min(-1) euglycemic insulin clamp (1200-1500 h) af ter oral placebo administration (at 0700 and 1100 h). Serum insulin (i mmunoreactive insulin) levels were significantly different in the thre e tests (12 +/- 2, 100 +/- 10, 194 +/- 19 pmol/L, P < 0.05), plasma FF A were low and similar (0.04 +/- 0.003, 0.02 +/- 0.005,0.02 +/- 0.003, not significant), and the GH response to GHRH was progressively lower (4871 +/- 1286, 2414 +/- 626, 1076 +/- 207 mu g/L.120 min), although only test 3 was significantly different from test 1 (P < 0.05). Poolin g the three tests together, a significant negative regression was obse rved between mean serum immunoreactive insulin levels and the GH respo nse to GHRH (r = -0.629, P < 0.01). Our results indicate that in healt hy subjects, acipimox and hyperinsulinemia produce a similar decrease in FFA levels and that at similar low FFA, the GH response to GHRH is lower during insulin infusion than after acipimox. These data suggest that insulin exerts a negative effect on GH release. Because the insul in levels able to reduce the GH response to GHRH are commonly observed during the day, for instance during the postprandial period, we concl ude that the insulin negative effect on GH release may have physiologi cal relevance.