Role of growth hormone in regulating lipolysis, proteolysis, and hepatic glucose production during fasting.
BACKGROUND
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).


METHODS
We conducted an open label in-patient study in the General Clinical Research Center at the University of Michigan.


METHODS
Six healthy, nonobese volunteers participated.


METHODS
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.
Sakharova
Alla A
AA
Division of Metabolism, Endocrinology, and Diabetes, 3920 Taubman Center, University of Michigan Medical Center, Ann Arbor, MI 48109-5354, USA.
Horowitz
Jeffrey F
JF
Surya
Sowmya
S
Goldenberg
Naila
N
Harber
Matthew P
MP
Symons
Kathy
K
Barkan
Ariel
A
D000328:Adult; D005260:Female; D005947:Glucose / Q000096:biosynthesis*; D013006:Growth Hormone; D019382:Human Growth Hormone / Q000502:physiology*; D006801:Humans; D008066:Lipolysis; D008099:Liver / Q000378:metabolism*; D008297:Male; D011506:Proteins / Q000378:metabolism*; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors
D011506:Proteins; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D013006:Growth Hormone; D005947:Glucose