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Simultaneously, [1-13C]acetate was administered for determination of de novo lipogenesis and fractional cholesterol synthesis rates by mass isotopomer distribution analysis. In a separate group of rats, Triton WR 1339 was injected for determination of hepatic VLDL-triglyceride production. S4048 infusion significantly decreased plasma glucose (\u221211%) and insulin (\u221248%) levels and increased hepatic G6P (201%) and glycogen (182%) contents. Hepatic triglyceride contents increased from 5.8 \u00b1 1.4 \u03bcmol\/g liver in controls to 20.6 \u00b1 5.5 \u03bcmol\/g liver in S4048-treated animals. De novo lipogenesis was increased &amp;gt;10-fold in S4048-treated rats, without changes in cholesterol synthesis rates. Hepatic mRNA levels of acetyl-CoA carboxylase and fatty acid synthase were markedly induced. Plasma triglyceride levels increased fourfold, but no differences in plasma cholesterol levels were seen. Surprisingly, hepatic VLDL-triglyceride secretion was not increased in S4048-treated rats. These studies demonstrate that inhibition of the G6Pase system leads to acute stimulation of fat synthesis and development of hepatic steatosis, without affecting hepatic cholesterol synthesis and VLDL secretion. The results emphasize the strong interactions that exist between hepatic carbohydrate and fat metabolism.<\/jats:p>","DOI":"10.2337\/diabetes.50.11.2591","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"2591-2597","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":52,"title":["Acute Inhibition of Glucose-6-Phosphate Translocator Activity Leads to Increased De Novo Lipogenesis and Development of Hepatic Steatosis Without Affecting VLDL Production in Rats"],"prefix":"10.2337","volume":"50","author":[{"given":"Robert H.J.","family":"Bandsma","sequence":"first","affiliation":[{"name":"Groningen University Institute for Drug Exploration, Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics, Academic Hospital Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coen H.","family":"Wiegman","sequence":"additional","affiliation":[{"name":"Groningen University Institute for Drug Exploration, Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics, Academic Hospital Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas W.","family":"Herling","sequence":"additional","affiliation":[{"name":"Aventis Pharma Germany, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Joerg","family":"Burger","sequence":"additional","affiliation":[{"name":"Aventis Pharma Germany, Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"ter Harmsel","sequence":"additional","affiliation":[{"name":"Groningen University Institute for Drug Exploration, Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics, Academic Hospital Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred J.","family":"Meijer","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Academic Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes A.","family":"Romijn","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Academic Hospital Leiden, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk-Jan","family":"Reijngoud","sequence":"additional","affiliation":[{"name":"Groningen University Institute for Drug Exploration, Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics, Academic Hospital Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folkert","family":"Kuipers","sequence":"additional","affiliation":[{"name":"Groningen University Institute for Drug Exploration, Center for Liver, Digestive and Metabolic Diseases, Department of Pediatrics, Academic Hospital Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031304104670000_R1","doi-asserted-by":"crossref","unstructured":"Efendic S, Karlander S, Vranic M: Mild type II diabetes markedly increases glucose cycling in the postabsorptive state and during glucose infusion irrespective of obesity. 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