Disease relevance of G6pc

• Similar insulin-induced hypoglycemia experiments performed in adrenalectomized rats did not induce any stimulation of G-6-Pase [1].
• The successful ultracytochemical localization of G-6-Pase in cultured hepatoma cells has not been reported previously [2].
• In conclusion, 1) BMOV inhibits PEPCK mRNA expression and activity by rapid mechanisms that are not reproduced simply by correction of hyperglycemia; and 2) BMOV inhibits G-6-Pase expression by complex mechanisms that depend, in part, on correction of hyperglycemia [3].
• Comparison of marker enzymes in cirrhotic livers and in tumors either with or without cirrhosis indicated that changes in cytochrome P450 and G-6-Pase were rather the results of parenchymal damage, while GGT was elevated only in tumorous livers [4].
• Mixed cell foci and hepatocellular adenomas developed within 22-30 weeks and exhibited a remarkable decrease of G6PASE activity, a strong increase of G6PDH, GAPDH, G3PDH and MDH activities as well as extremely high ALKPASE and GGT activities [5].

High impact information on G6pc

• Cytochemically, the amount of the G-6-Pase reaction product in both forms of the tumor cells was obviously less than that in the normal hepatocytes [2].
• Overall, a 76% increase in the activity ratio G-6-Pase/GK was observed, which would favor net hepatic glucose release and elevated HGP in HFF rats [6].
• Administration of insulin to these animals also caused a decrease in G-6-Pase activity, which was most pronounced in the smooth microsomes [7].
• We interpret these results to indicate that diabetes causes hepatocytes to form additional smooth endoplasmic reticulum with specialized membranes, at least with respect to G-6-Pase [7].
• The results of cell fractionation indicate that membranes of the smooth endoplasmic reticulum are enriched in G-6-pase [7].

Chemical compound and disease context of G6pc

• This study was conducted to test the hypothesis of the activation of glucose-6-phosphatase (G-6-Pase) in situations where the liver is supposed to sustain high glucose supply, such as during the counterregulatory response to hypoglycemia [1].
• Activation of liver G-6-Pase in response to insulin-induced hypoglycemia or epinephrine infusion in the rat [1].

Biological context of G6pc

• Loss of DG-6-P was modeled as a two-step process: (a) transfer of DG-6-P from the cytosol into the cisterns of the endoplasmic reticulum; (b) hydrolysis of DG-6-P by G-6-Pase and subsequent return of the free DG to the precursor pool [8].
• Thus short-term, chronic exposure to HSD and HFD increase in vivo gluconeogenesis and the G-6-Pase catalytic subunit [9].
• Triamcinolone (20 microgram per fetus) administered in utero to term rat fetuses (day 21 of gestation) increases the activities of renal G-6-Pase and PEPCK [10].
• Hepatocyte cell suspensions were used to ascertain whether diet-induced adaptations in glucose phosphorylation and GK might serve to compensate for upregulation of G-6-Pase [9].
• However, the cytochrome was destroyed under anaerobic conditions in which lipid peroxidation and loss of G-6-Pase were greatly suppressed [11].

Anatomical context of G6pc

• These results indicate negligible G-6-Pase activity in cultured astrocytes [12].
• Parathormone (1 unit per fetus) administered to decapitated fetuses completely restores the G-6-Pase activity [10].
• G-6-Pase activity was significantly higher in HSD and HFD vs. STD in both intact and disrupted liver microsomes [9].
• However, the decrease in microsomal G-6-Pase activity by CCl4 treatment was not prevented by eugenol suggesting that the damage to endoplasmic reticulum is not protected [13].
• Glucose-6-phosphatase (G-6-Pase) hydrolyzes glucose-6-phosphate to glucose, reciprocal with the so-called glucose sensor, glucokinase, in pancreatic beta cells [14].

Associations of G6pc with chemical compounds

• Infusion of epinephrine (1 microg x kg(-1) x min(-1)) in normal rats induced a dramatic 80% increase in EGP and a 60% increase in G-6-Pase activity [1].
• 2-Deoxyglucose-6-phosphate (DG-6-P) may therefore have limited access to glucose-6-phosphatase (G-6-Pase), and transport of the DG-6-P across the endoplasmic reticular membrane may be rate limiting to its dephosphorylation [8].
• A detailed kinetic analysis of G-6-Pase activity has been performed to distinguish between effects on the microsomal carrier for glucose-6-phosphate and those on the enzyme itself [15].
• These differences could not be explained by changes in the response of isolated microsomes to sodium deoxycholate or by effects on the energy of activation of G-6-Pase [15].
• Phlorizin corrected plasma glucose but had no effect on PEPCK mRNA and only partially normalized G-6-Pase mRNA [3].

Other interactions of G6pc

• In these models, morphology, tumor incidence as well as polysubstrate monooxygenase system, gamma-glutamyltransferase (GGT) and glucose-6-phosphatase (G-6-Pase) were studied [4].
• In the livers of T-1095-treated ZDF rats, hepatic glucose production rate (HGP) and glucose utilization rate (GUR) showed marked recovery, with almost complete normalization of reduced glucokinase/glucose-6-phosphatase (G-6-Pase) activities ratio [16].
• As pancreatectomized foetuses develop sub-normal liver G-6-Pase activity, glucagon is probably not responsible for the increase in this activity occurring during normal development before birth [17].
• In addition, diminution or depletion of glycogen, reduction of catalase-containing peroxisomes, increase of G-6-Pase activity, and depletion of cytochrome c oxidase in many mitochondria were also observed in hepatocytes of experimental animals [18].
• The overall results suggest that LPS stimulates: (a) hepatic synthesis and secretion of fibronectin; (b) uptake of calcium by hepatocytes; and (c) G-6-Pase activity [18].

Analytical, diagnostic and therapeutic context of G6pc

• G6PASE and GGT remained elevated up to 72 h before dropping to normal at 20 days after treatment [19].
• From Northern blot and enzymatic studies, we report that only phosphoenolpyruvate carboxykinase (PEPCK) activity is induced at 24 h of fasting, whereas glucose-6-phosphatase (G-6-Pase) activity is induced only from 48 h [20].
• After partial hepatectomy, rat hepatic G-6-Pase gene expression is transcriptionally regulated, and mRNA levels are increased approximately 30-fold [21].
• It is pointed out that accurate biochemical determinations of G-6-Pase activity will critically depend on painstaking microdissection of nuclei and cell layers [22].
• The establishment of a breeding colony of this dog strain will facilitate studies on the role of G-6-Pase gene in glucose homeostasis, in pathophysiology of disease, and development of novel therapeutic approaches such as gene therapy [23].

References