Context: Fasting is associated with suppressed insulin and augmented growth hormone (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 days of complete fasting, using a model of selective GH suppression by the administration of GH-releasing hormone receptor antagonist (GHRH-A).

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

Participants: Six healthy, non-obese volunteers.

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

Results: GHRH–A suppressed plasma GH by 65% during the fed state (p=0.015), but did not alter the rates of lipolysis, proteolysis, or HGP. Fasting for 2 days suppressed plasma insulin concentration by 80% and elevated plasma GH 4-fold (both p<0.01). This was accompanied by a doubling in the rate of lipolysis, 40% increase in proteolysis and 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 very limited metabolic role during the daily feed/fast cycle but is essential for the increased lipolytic rate found with more prolonged fasting.