Compartmentation of glucose 6-phosphate in hepatocytes

Kalant, N.; Parniak, Michael A.; Lemieux, Melissa

doi:10.1042/bj2520932b

Cited by 5 publications

(4 citation statements)

References 2 publications

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“…In hepatocytes sub-compartmentation of cytosolic glucose-6-phosphate pool has been supposed. Based on various observations it has been described that one of the glucose-6-phosphate pools is functionally linked to glycogenolysis, while the other one is connected to gluconeogenesis [1,11,12]. The hypothesis on different glucose-6-phosphate pools and the supporting data are in agreement with the findings, that glucose uptake or gluconeogenesis are unable to cover the cofactor supply for glucuronidation and ascorbate production.…”

Section: Glycogen Particles and The Luminal Compartment Of The Endoplsupporting

confidence: 72%

Role of glutathione in the regulation of liver metabolism

Mandl

Bánhegyi

2003

BioFactors

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Section: Glycogen Particles and The Luminal Compartment Of The Endoplsupporting

confidence: 72%

Role of glutathione in the regulation of liver metabolism

Mandl

Bánhegyi

2003

BioFactors

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“…This nuclear localization might be of interest as it has been demonstrated that glucokinase activity (the reaction opposite to that of Glc6Pase in liver) is regulated by an intranuclear protein [27] and its translocation from the nucleus to the cytosol increases in the presence of high glucose concentration (20±30 mm) [28,29] and fructose 1-phosphate [27,30,31]. It is also well known that Glc6P in hepatocytes is not a homogeneous pool but seems to be associated with different cell compartments where glucose phosphorylation, gluconeogenesis or glycogenolysis take place [32].…”

Section: Localizationmentioning

confidence: 99%

New lessons in the regulation of glucose metabolism taught by the glucose 6‐phosphatase system

Werve¹,

Lange

Newgard³

et al. 2000

European Journal of Biochemistry

130

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The operation of glucose 6-phosphatase (EC 3.1.3.9) (Glc6Pase) stems from the interaction of at least two highly hydrophobic proteins embedded in the ER membrane, a heavily glycosylated catalytic subunit of m 36 kDa (P36) and a 46-kDa putative glucose 6-phosphate (Glc6P) translocase (P46). Topology studies of P36 and P46 predict, respectively, nine and ten transmembrane domains with the N-terminal end of P36 oriented towards the lumen of the ER and both termini of P46 oriented towards the cytoplasm. P36 gene expression is increased by glucose, fructose 2,6-bisphosphate (Fru-2,6-P2) and free fatty acids, as well as by glucocorticoids and cyclic AMP; the latter are counteracted by insulin. P46 gene expression is affected by glucose, insulin and cyclic AMP in a manner similar to P36. Accordingly, several response elements for glucocorticoids, cyclic AMP and insulin regulated by hepatocyte nuclear factors were found in the Glc6Pase promoter. Mutations in P36 and P46 lead to glycogen storage disease (GSD) type-1a and type-1 non a (formerly 1b and 1c), respectively. Adenovirus-mediated overexpression of P36 in hepatocytes and in vivo impairs glycogen metabolism and glycolysis and increases glucose production; P36 overexpression in INS-1 cells results in decreased glycolysis and glucose-induced insulin secretion. The nature of the interaction between P36 and P46 in controling Glc6Pase activity remains to be defined. The latter might also have functions other than Glc6P transport that are related to Glc6P metabolism.

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“…There is strong evidence that D-glucose does not have free access to the whole intracellular water space (31). In this sense, cytosolic concentrations of free molecules of D-glucose and/or ~-glucose-6-phosphate are kept within a certain physiological range by a complex mechanism involving metabolism and cellular compartmentation (32). An impairment of this mechanism may thus alter the osmotic balance within the cell.…”

Section: Bile Flow (Pl/min/g Liver)mentioning

confidence: 99%

Hyperglycemia-induced cholestasis in the isolated perfused rat liver

et al. 1991

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In a previous report we showed that cholestasis in diabetic rats is due in part to hyperglycemia. To gain information about the mechanism responsible for this phenomenon, bile flow was studied in isolated perfused rat livers. The perfusion media were modified erythrocyte-free Krebs-Henseleit solutions. Under these experimental conditions, no cholestasis was observed in isolated rat livers obtained from rats treated with streptozotocin (6 mg/100 gm body wt) 6 days before the experiments. We then proceeded to use normal animals. The composition of the perfusion media was modified to maintain the osmolality even after increasing D-glucose concentrations from 0 to 35 mmol/L. Bile flow was not affected with doses up to 15 mmol/L D-glucose. Beyond a threshold value for plasma D-glucose concentrations between 15 and 20 mmol/L, cholestasis was observed. Using D-glucose analogs such as L-glucose and 3-O-methyl-D-glucose, bile flow was also reduced (by 0.54 and 0.53 microliters/min/gm liver, respectively). Isosmotic sucrose-containing perfusion media were also observed to impair bile flow (by 0.66 microliters/min/gm liver). However, i-erythritol and D-mannitol failed to inhibit bile formation. The study of bile/plasma concentration ratios determined using tracer amounts of radioactive sugars indicated that this value was much lower for cholestatic sucrose (0.11) and L-glucose (0.31) than for noncholestatic i-erythritol (0.99) and D-mannitol (0.98). Cholestasis was partly reversed after induction by 35 mmol/L D-glucose if perfusion media were replaced by sugar-free ones, but also by media containing 25 mmol/L D-glucose. Insulin given during the perfusion with sugar-free media was observed to have no effect on bile flow.(ABSTRACT TRUNCATED AT 250 WORDS)

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Compartmentation of glucose 6-phosphate in hepatocytes

Cited by 5 publications

References 2 publications

Role of glutathione in the regulation of liver metabolism

Role of glutathione in the regulation of liver metabolism

New lessons in the regulation of glucose metabolism taught by the glucose 6‐phosphatase system

Hyperglycemia-induced cholestasis in the isolated perfused rat liver

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