2001
DOI: 10.2337/diabetes.50.11.2591
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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

Abstract: Glucose-6-phosphatase (G6Pase) is a key enzyme in hepatic glucose metabolism. Altered G6Pase activity in glycogen storage disease and diabetic states is associated with disturbances in lipid metabolism. We studied the effects of acute inhibition of G6Pase activity on hepatic lipid metabolism in nonanesthetized rats. Rats were infused with an inhibitor of the glucose-6-phosphate (G6P) translocator (S4048, 30 mg ⅐ kg -1 ⅐ h -1 ) for 8 h. Simultaneously, [1-13 C]acetate was administered for determination of de no… Show more

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Cited by 61 publications
(71 citation statements)
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“…Cellular cholesterol synthesis is under control of SREBP-2, which becomes inactivated by increased intracellular sterol contents (31). However, we did not find an increase in cholesterol synthesis rates in an acute animal model of GSD-1 (17). This might indicate that increased cholesterol synthesis in GSD-1a patients might be caused by indirect mechanisms, although a role of SREBP-2 cannot be excluded.…”
Section: Discussioncontrasting
confidence: 52%
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“…Cellular cholesterol synthesis is under control of SREBP-2, which becomes inactivated by increased intracellular sterol contents (31). However, we did not find an increase in cholesterol synthesis rates in an acute animal model of GSD-1 (17). This might indicate that increased cholesterol synthesis in GSD-1a patients might be caused by indirect mechanisms, although a role of SREBP-2 cannot be excluded.…”
Section: Discussioncontrasting
confidence: 52%
“…This increased flux, leading to increased production of acetyl-CoA, which is the precursor for cholesterogenesis and de novo lipogenesis, could possibly stimulate de novo lipogenesis directly, although no evidence is present to support this. However, in an acute animal model of GSD-1, cholesterol synthesis was not stimulated despite an increased production acetyl-CoA (17).…”
Section: Discussionmentioning
confidence: 99%
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“…Evidence can be adduced that intracellular G6P resides in several separate non-homogenous compartments, with distinct pools even within the cytosol (Christ & Jungermann 1987, Kalant et al 1988, Seoane et al 1996, Bandsma et al 2001, Meijer 2002. After entry into the ER, it is uncertain as to whether the G6P exists in a single pool, accessible equally to two luminal enzymes, G6Pase and H6PDH.…”
Section: Appendixmentioning
confidence: 99%
“…H6PDH is a bifunctional enzyme exhibiting both hexose-6-phosphate dehydrogenase and 6-phosphogluconolactonase activities, in relation to the oxidative segment of the cytosolic pentose pathway. Although there is a wide distribution of tissues, the highest activity is found in the liver (Tanahashi & Hori 1980, Mandula et al 1970, Blume et al 1975, Barash et al 1990. By generating NADPH, this enzyme governs the redox state of the luminal pyridine nucleotides, a pool that is kinetically, and possibly structurally, shared by 11β-HSD1.…”
Section: Introductionmentioning
confidence: 99%