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Role of Growth Hormone in Regulating Lipolysis, Proteolysis, and Hepatic Glucose Production during Fasting

Division of Metabolism, Endocrinology, and Diabetes (A.A.S., S.S., N.G., K.S., A.B.), Division of Kinesiology (J.F.H., M.P.H.), and the Department of Neurosurgery (A.B.), University of Michigan Medical Center and the Ann Arbor Department of Veterans Affairs (DVA) Medical Center, Ann Arbor, Michigan 48109

Address all correspondence and requests for reprints to: Ariel Barkan, M.D., Division of Metabolism, Endocrinology, and Diabetes, 3920 Taubman Center, SPC 5354, University of Michigan Medical Center, Ann Arbor, Michigan 48109-5354. E-mail: abarkan{at}umich.edu.

Context: Fasting is associated with suppressed insulin and augmented GH secretion. The involvement of each mechanism in the regulation of fuel mobilization during fasting is unknown.

Objective: To ascertain the role of GH in the regulation of the rates of lipolysis, proteolysis, and hepatic glucose production (HGP) during the physiological daily feed/fast cycle and after 2 d of complete fasting, we used a model of selective GH suppression by the administration of GHRH receptor antagonist (GHRH-A).

Design and Setting: We conducted an open label in-patient study in the General Clinical Research Center at the University of Michigan.

Participants: Six healthy, nonobese volunteers participated.

Main Outcome Measures: We assessed 24-h plasma GH concentration and rates of lipolysis, proteolysis, and HGP using stable isotope techniques after an overnight fast and after 2 d of fasting.

Results: GHRH-A suppressed plasma GH by about 65% during the fed state (P = 0.015) but did not alter the rates of lipolysis, proteolysis, or HGP. Fasting for 2 d suppressed plasma insulin concentration by about 80% and elevated plasma GH about 4-fold (both P < 0.01). This was accompanied by a doubling in the rate of lipolysis, an approximately 40% increase in proteolysis, and an approximately 30% decline in HGP (all P < 0.05). Preventing the fasting-induced increase in GH with GHRH-A largely abolished the increase in the rate of lipolysis. GHRH-A also augmented the fasting-induced reduction in HGP but did not alter proteolysis.

Conclusions: Endogenous GH plays a very limited metabolic role during the daily feed/fast cycle but is essential for the increased lipolytic rate found with more prolonged fasting.