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Evidence for an Inhibitory Effect of Physiological Levels of Insulin on the Growth Hormone (GH) Response to GH-Releasing Hormone in Healthy Subjects

Istituto Scientifico San Raffaele, Cattedra di Medicina Interna (R.L., M.F.M., A.C.A., M.E.M., E.B., L.P.S., L.L., A.E.P.); Unità di Bioingegneria (A.C.), Università degli Studi di Milano, 20132 Milan, Italy

Address all correspondence and requests for reprints to: Roberto Lanzi, M.D., Istituto Scientifico San Raffaele, Via Olgettina 60, 20132 Milano, Italy.

It has been previously reported that in healthy subjects, the acute reduction of free fatty acids (FFA) levels by acipimox enhances the GH response to GHRH. In the present study, the GH response to GHRH was evaluated 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 µg iv, at 1300 h) during: 1) iv 0.9% NaCl infusion (1200–1500 h) after oral acipimox administration (250 mg) at 0700 h and at 1100 h; 2) 0.1 mU·kg^-1·min^-1 euglycemic insulin clamp (1200–1500 h) after oral acipimox administration (250 mg at 0700 h and at 1100 h); 3) 0.4 mU·kg^-1·min^-1 euglycemic insulin clamp (1200–1500 h) after oral placebo administration (at 0700 and 1100 h).

Serum insulin (immunoreactive insulin) levels were significantly different in the three tests (12 ± 2, 100 ± 10, 194 ± 19 pmol/L, P < 0.05), plasma FFA 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 µg/L·120 min), although only test 3 was significantly different from test 1 (P < 0.05). Pooling the three tests together, a significant negative regression was observed between mean serum immunoreactive insulin levels and the GH response to GHRH (r = -0.629, P < 0.01).

Our results indicate that in healthy 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 insulin levels able to reduce the GH response to GHRH are commonly observed during the day, for instance during the postprandial period, we conclude that the insulin negative effect on GH release may have physiological relevance.

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