L. Guignot et G. Mithieux, Mechanisms by which insulin, associated or not with glucose, may inhibit hepatic glucose production in the rat, AM J P-ENDO, 277(6), 1999, pp. E984-E989
Citations number
25
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
We investigated the intrahepatic mechanisms by which insulin, associated or
not with hyperglycemia, may inhibit hepatic glucose production (HGP) in th
e rat. After a hyperinsulinemic euglycemic clamp in postabsorptive (PA) ane
sthetized rats, the 70% inhibition of HGP could be explained by a dramatic
decrease in the glucose 6-phosphate (G-6-P) concentration, whereas the gluc
ose-6-phosphatase (G-6-Pase) and glucokinase (GK) activities were unchanged
. Under hyperinsulinemic hyperglycemic condition, the GK flux was increased
. The G-6-P concentration was not or only weakly decreased. The inhibition
of HGP involved a significant 25% inhibition of the G-6-Pase activity. Unde
r similar conditions in fasted rats, the GK flux was very low. The suppress
ion of G-6-Pase and HGP did not occur, despite plasma insulin and glucose c
oncentrations similar to those in PA rats. Therefore, 1) insulin suppresses
HGP in euglycemia by solely decreasing the G-6-P concentration; 2) when co
mbining both hyperinsulinemia and hyperglycemia, the suppression of HGP inv
olves the inhibition of the G-6-Pase activity; and 3) a sustained glucose-p
hosphorylation flux might be a crucial determinant in the inhibition of G-6
-Pase and of HGP.