Activation of liver G-6-Pase in response to insulin-induced hypoglycemia or epinephrine infusion in the rat.
This study was conducted to test the hypothesis of the activation of glucose-6-phosphatase (G-6-Pase) in situations where the liver is supposed to sustain high glucose supply, such as during the counterregulatory response to hypoglycemia. Hypoglycemia was induced by insulin infusion in anesthetized rats. Despite hyperinsulinemia, endogenous glucose production (EGP), assessed by [3-(3)H]glucose tracer dilution, was paradoxically not suppressed in hypoglycemic rats. G-6-Pase activity, assayed in a freeze-clamped liver lobe, was increased by 30% in hypoglycemia (P < 0.01 vs. saline-infused controls). Infusion of epinephrine (1 microg x kg(-1) x min(-1)) in normal rats induced a dramatic 80% increase in EGP and a 60% increase in G-6-Pase activity. In contrast, infusion of dexamethasone had no effect on these parameters. Similar insulin-induced hypoglycemia experiments performed in adrenalectomized rats did not induce any stimulation of G-6-Pase. Infusion of epinephrine in adrenalectomized rats restored a stimulation of G-6-Pase similar to that triggered by hypoglycemia in normal rats. These results strongly suggest that specific activatory mechanisms of G-6-Pase take place and contribute to EGP in situations where the latter is supposed to be sustained.
Bady
Isabelle
I
Institut National de la Santé et de la Recherche Médicale U. 449, Faculté de Médecine Laennec, 69372 Lyon, France.
Zitoun
Carine
C
Guignot
Ludovic
L
Mithieux
Gilles
G
D000315:Adrenalectomy; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology; D005947:Glucose / Q000096:biosynthesis; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D007003:Hypoglycemia / Q000139:chemically induced / Q000201:enzymology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D005938:Glucocorticoids; D007328:Insulin; D003907:Dexamethasone; D005952:Glucose-6-Phosphatase; D005947:Glucose; D004837:Epinephrine