LIVER GLUCOSE-6 PHOSPHATASE-ACTIVITY IS INHIBITED BY REFEEDING IN RATS

This study was conducted to determine whether inhibition of hepatic gl ucose-6 phosphatase is involved in the mechanism of suppression of hep atic glucose production during the postprandial period. We studied the time course of changes in the enzyme activity by refeeding food-depri ved rats with nonpurified diet. The V-max the enzyme, assayed in homog enates from livers freeze-clamped in situ in anesthetized 48-h unfed r ats (12.3 +/- 0.15 U/g wet liver, mean +/- SEM, n = 6) was progressive ly decreased upon refeeding: 11.1 +/- 0.5, 8.5 +/- 0.4 and 7.9 +/- 0.5 U/g, in rats refed for 90, 180 (P < 0.01) and 360 min (P ( 0.01), res pectively. The Km of the enzyme was not affected by refeeding. No inhi bition of the enzyme was observed in microsomes purified from these ho mogenates, suggesting a metabolite-induced inhibition mechanism. To as sess the role of insulin in the inhibition, we assayed the glucose-6 p hosphatase activity in similarly processed liver homogenates from food -deprived rats perfused with insulin at physiological and supraphysiol ogical concentrations, whereas plasma glucose was maintained at the ba sal level by adapted glucose perfusion (euglycemic clamps). No inhibit ion of glucose-6 phosphatase was found under these conditions, suggest ing that insulin cannot by itself account for the inhibition observed in the refeeding experiments. These data constitute the first demonstr ation of the inhibition of glucose-6 phosphatase activity during the p ostprandial period.