Liver microsomal glucose-6-phosphatase is competitively inhibited by the lipid products of phosphatidylinositol 3-kinase.

The Journal of Biological Chemistry
Gilles MithieuxCarine Zitoun

Abstract

We have studied the effect of various phospholipids on the activity of glucose-6-phosphatase (Glc6Pase) in untreated and detergent-treated rat liver microsomes. Glc6Pase is inhibited in the presence of phosphoinositides in a dose-dependent manner within a range of concentration 0.5-10 microM. The order of efficiency in untreated microsomes is: phosphatidylinositol (PI) 3,4,5P3 > PI3,4P2 = PI4,5P2 > PI3P = PI4P > PI. In contrast, Glc6Pase is not inhibited in the presence of phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine, diacylglycerol, and inositol 1,4, 5-trisphosphate at concentrations up to 100 microM. The mechanism of Glc6Pase inhibition by PI4,5P2, PI3,4P2, and PI3,4,5P3 is competitive in both untreated and detergent-treated microsomes. In untreated microsomes, the Ki for PI3,4,5P3 (1.7 +/- 0.3 microM, mean +/- S.D. n = 3) is significantly lower (p < 0.01) than that for PI3, 4P2 (5.0 +/- 0.8 microM) and for PI4,5P2 (4.7 +/- 0.7 microM). In detergent-treated microsomes, Glc6Pase is less sensitive to the inhibition and there is no difference anymore among the Ki values for the three compounds: 8.3 +/- 0.8, 11.1 +/- 0.5 and 8.9 +/- 0.4 microM for PI3,4,5P3, PI3,4P2, and PI4,5P2, respectively. This inhibi...Continue Reading

References

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Citations

Apr 5, 2002·Chembiochem : a European Journal of Chemical Biology·Albert Jeltsch
Oct 25, 2002·Diabetes/metabolism Research and Reviews·Silvia Mora, Jeffrey E Pessin
Sep 6, 2002·Journal of Peptide Science : an Official Publication of the European Peptide Society·Anna Maria DursiPaolo Rovero
Mar 7, 2002·The Biochemical Journal·Emile van Schaftingen, Isabelle Gerin
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Sep 21, 2013·Lipids in Health and Disease·Uberdan Guilherme Mendes de CastroAndréia Carvalho Alzamora
Apr 11, 2014·Kidney International·Julie ClarFabienne Rajas
Jun 28, 2014·Diabetes Research and Clinical Practice·Gilles Mithieux, Amandine Gautier-Stein
Aug 22, 2001·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·R M BezerraJ A Gontijo
Dec 6, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·Chang An ChuMasakazu Shiota
Jan 30, 2009·American Journal of Physiology. Endocrinology and Metabolism·Kazutaka AokiYasuo Terauchi
Mar 8, 2002·American Journal of Physiology. Endocrinology and Metabolism·Isabelle BadyGilles Mithieux
Sep 25, 1999·The Journal of Biological Chemistry·L LavoieB I Posner
Dec 12, 2001·American Journal of Physiology. Endocrinology and Metabolism·Michael J PagliassottiMichael E Bizeau
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Nov 26, 2020·Metabolism Open·Toyin Mohammed SalmanSheu Oluwadare Sulaiman
Jun 1, 2001·Cellular Signalling·B PayrastreM Gratacap

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