Effect of growth hormone deficiency on hormonal control of hepatic glycogenolysis in hypophysectomized rat.
The present study was designed to investigate the hormonal regulation of rat liver glycogenolysis in growth hormone (GH) deficiency. To this end, hepatocytes were isolated from control, GH-deprived (hypophysectomized and treated with triiodothyronine [T3] and corticotropin), and 7-day GH-supplemented fed rats and incubated with glucagon and alpha 1-adrenergic agonist (phenylephrine) to measure the hormonal activation of both glycogen phosphorylase and glucose production from glycogen stores. GH deficiency induces a combined decrease of 50% of the glycogen content, the activity of glucose-6-phosphatase, and the maximal hormone-induced glycogen phosphorylase activity. Daily GH injections restore the levels of both glycogen phosphorylase and glucose-6-phosphatase. These enzymatic inductions occur without normalization of insulinemia. Despite the reduced levels of key enzymes of glycogenolysis, the stimulation of glucose production from glycogen in response to glucagon and phenylephrine is not modified in GH-deprived rats. An increase in the intrinsic activity of one or both of the enzymatic steps is postulated to compensate for the lower levels of enzymes, as indicated by the slopes of the correlation between glucose production and phosphorylase a activity (107 and 216 nmol glucose produced/min/U phosphorylase a [P < .001] in control and GH-deprived rats, respectively). GH replacement enhances maximal phosphorylase activity and brings the correlation toward the control value (slope, 128 nmol glucose produced/min/U phosphorylase a). Our findings demonstrate that glycogenolysis in hepatocytes isolated from GH-deprived rats is normal, despite a reduction of glycogen phosphorylase and glucose-6-phosphatase activities.(ABSTRACT TRUNCATED AT 250 WORDS)
Vidal
H
H
INSERM U 197, Faculté de Médecine Alexis Carrel, Lyon, France.
Géloën
A
A
Minaire
Y
Y
Riou
J P
JP
D000818:Animals; D004789:Enzyme Activation; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D013006:Growth Hormone / Q000172:deficiency*; D006728:Hormones / Q000502:physiology*; D007016:Hypophysectomy; D008099:Liver / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D010762:Phosphorylase a / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005958:Glucosephosphates; D006728:Hormones; D010656:Phenylephrine; D019298:Glucose-6-Phosphate; D013006:Growth Hormone; D006003:Glycogen; D005934:Glucagon; D010762:Phosphorylase a; D005947:Glucose