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Mediation of the Hepatic Effects of Growth Hormone by Its Lipolytic Activity

Istituto Scientifico H. San Raffaele, Unita’ di Malattie Metaboliche, Cattedra di Medicina Interna; Divisione di Medicina, Cattedra di Clinica Medica (L.D.M., G.V.); Laboratorio di Spettrometria di Massa (F.M.); Divisione di Statistica ed Epidemiologia (A.C.); and Dipartimento di Chimica e Biochimica Medica (M.G.-K.), University of Milan, 20132 Milan; and IRCCS H. San Raffaele, Milan, Italy

Address all correspondence and requests for reprints to: Pier Marco Piatti, M.D., Istituto H. Scientifico San Raffaele, Via Olgettina 60, 20132 Milan, Italy.

The aim of the study was to investigate the acute effect of GH per se, independent from its lipolytic activity, on glucose and lipid oxidation and glucose turnover in seven healthy subjects. Five tests lasting 360 min were performed. Each test consisted of a 4-h equilibration period followed by a euglycemic hyperinsulinemic (25 mU/kg·h) clamp lasting 2 h. In test 1 (control experiment) saline was infused, leaving GH and FFA at basal levels. In tests 2, 3, and 4, GH was infused (80 ng/kg·min) to increase GH levels. Whereas in test 2 FFA levels were free to increase due to GH lipolytic activity, in test 3 FFA elevation was prevented by using an antilipolytic compound (Acipimox) that allowed evaluation of the effect of GH at low FFA levels. In test 4 (GH+Acipimox+heparin) GH infusion was associated with the administration of Acipimox and heparin to maintain FFA at the basal level to evaluate the effect of GH per se independent from GH lipolytic activity. In test 5 Acipimox and a variable heparin infusion were given to evaluate possible effects of Acipimox other than the inhibition of lipolysis.

During the euglycemic hyperinsulinemic clamp in the presence of high GH and FFA levels (test 2), glucose oxidation was significantly lower and lipid oxidation was significantly higher than in tests 1, 3, 4, and 5. During the same period, hepatic glucose production was completely suppressed in the control study (test 1; 94%) and in test 5 (99.6%), whereas it was significantly less inhibited (65%, 74%, and 73%) when GH was administered in tests 2, 3, and 4.

In conclusion, these results suggest that GH directly mediates the reduction of insulin’s effect on the liver. In addition, the effect of GH on glucose and lipid oxidation is not direct, but is mediated by its lipolytic activity.

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