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Liver Glucose-6 Phosphatase Activity is Inhibited by Refeeding in Rats^1,2,

Institut National de la Santé et de la Recherche Médicale, Unités 197 ^* 331, Faculté de Médecine Alexis Carrel, 69372 Lyon Cédex 08, France

This study was conducted to determine whether inhibition of hepatic glucose-6 phosphatase is involved in the mechanism of suppression of hepatic glucose production during the postprandial period. We studied the time course of changes in the enzyme activity by refeeding food-deprived rats with nonpurified diet. The V_max of the enzyme, assayed in homogenates from livers freeze-clamped in situ in anesthetized 48-h unfed rats (12.3 ± 0.15 U/g wet liver, mean ± SEM, n = 6) was progressively 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), respectively. The Km of the enzyme was not affected by refeeding. No inhibition of the enzyme was observed in microsomes purified from these homogenates, suggesting a metabolite-induced inhibition mechanism. To assess the role of insulin in the inhibition, we assayed the glucose-6 phosphatase activity in similarly processed liver homogenates from food-deprived rats perfused with insulin at physiological and supraphysiological concentrations, whereas plasma glucose was maintained at the basal level by adapted glucose perfusion (euglycemic clamps). No inhibition of glucose-6 phosphatase was found under these conditions, suggesting that insulin cannot by itself account for the inhibition observed in the refeeding experiments. These data constitute the first demonstration of the inhibition of glucose-6 phosphatase activity during the postprandial period.

KEY WORDS: • glucose-6 phosphatase • liver • refeeding • insulin • rats

¹ Supported by the "Institut National de la Santé et de la Recherche Médicale."

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ Recipients of grants from the French "Ministee de l'Enseignement Supeieur et de la Recherche."

⁴ To whom correspondence should be addressed.

Manuscript received 1 May 1995. Revision accepted 13 June 1995.

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