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1-propyl-3-(pyridin-2-yl)thiourea
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40.71% inhibition
1-[(4'-O-(E)-p-coumaroyl)-beta-D-glucopyranosyl]-oxy-2-phenol
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1-[(6'-O-(E)-p-coumaroyl)-beta-D-glucopyranosyl]-oxy-2-phenol
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1-[O-beta-D-glucopyranosyl(1->2)-beta-D-glucopyranosyl]-oxy-2-phenol
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2-nitro-5-thiocyano-benzoic acid
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2-oxoglutarate
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in complex with Mg2+, inhibition at low substrate concentrations, inhibition of the translocase component of the glucose 6-phosphatase system
2-{[bis(hydrazine)methylene]amino}-4-methylpentanoic acid
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2.61% inhibition
2-{[bis(hydrazino)methylene]amino}-3-(4-hydroxyphenyl)propanoic acid
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6.61% inhibition
2-{[bis(hydrazino)methylene]amino}-3-hydroxybutanoic acid
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11.68% inhibition
2-{[bis(hydrazino)methylene]amino}-3-hydroxypropanoic acid
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10.56% inhibition
2-{[bis(hydrazino)methylene]amino}-3-methylpentanoic acid
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3.37% inhibition
3,4-dicaffeoylquinic acid
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3,4-dichlorobenzaldehyde dibenzylhydrazone
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3-Mercaptopicolinic acid
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inhibitor of D-glucose 6-phosphate translocase
3-methoxybenzaldehyde dibenzylhydrazone
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4,4'-di-isothiocyanostilbene-2,2'-disulphonate
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inhibitor of D-glucose 6-phosphate translocase
4,5-dicaffeoylquinic acid
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4-(beta-D-glucopyranosyloxy) benzoic acid
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4-caffeoylquinic acid
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4-chlorobenzaldehyde dibenzylhydrazone
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4-hydroxybenzaldehyde dibenzylhydrazone
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4-maleimidylstilbene-2,2'-disulfonic acid
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4-methoxybenzaldehyde dibenzylhydrazone
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4-methoxyphenyl-[4-(4-methoxyphenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl]methanone
4-methoxyphenyl-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl]methanone
5-((((iodoacetyl)amino)ethyl)amino)naphthalene-1-sulfonic acid
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5-caffeoylquinic acid
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5-chlorotetrahydrothiophene-2-carbaldehyde dibenzylhydrazone
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5-ethyltetrahydrofuran-2-carbaldehyde dibenzylhydrazone
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alpha-phosphatidylinositol 3-monophosphate
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alpha-phosphatidylinositol 4,5-diphosphate
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alpha-phosphatidylinositol 4-monophosphate
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apigenin-7-O-beta-D-glucopyranoside
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apigenin-7-O-beta-D-glucuronic acid-6''-methyl ester
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benzaldehyde dibenzylhydrazone
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CoA
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inhibits enzyme activity in intact microsomes
EGTA
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inhibits enzyme activity in histone 2A-treated or alamethicin-treated microsomes, but has little effect on enzyme activity in intact microsomes
epicatechin gallate
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acts similarly but less efficiently than epigallocatechin gallate
epigallocatechin gallate
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increases latency of G6Pase, inhibitory effect is greater in intact than in permeabilized microsomes. It does not hinder microsomal D-glucose 6-phosphate uptake. Reduces activity of G6Pase through the inhibition of glucose efflux from the endoplasmic reticulum lumen; inhibition of enzyme in intact, but not in permeabilized microsome. Epigallocatechin gallate does not hinder microsomal glucose uptake, but inhibits microsomal glucose efflux thus inhibiting the enzyme through an elevated luminal glucose level
fatty-acyl-CoA
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with chain-length equal to or higher than 16, at 0.001-0.002 mM, the inhibitory effect on the enzyme of untreated microsomes is either partially or totally cancelled, or even changes into an activation effect at higher concentrations, the inhibition is fully reversible in presence of bovine serum albumin. With medium chain-length, 10-14 carbons inhibit the enzyme of untreated microsomes in a dose-dependent manner in the range 0.001-0.02 mM, the higher the chain length, the stronger the inhibitory effect
gallocatechin gallate
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increases latency of G6Pase, inhibitory effect is greater in intact than in permeabilized microsomes
Insulin
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insulin causes a decrease in the activity of enzyme in the liver in vivo
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isonicotinaldehyde dibenzylhydrazone
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L-alpha-phosphatidylinositol 3,4,5-trisphosphate
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L-alpha-phosphatidylinositol 3,4-diphosphate
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myristoyl-CoA
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uncompetitive inhibition of enzyme in untreated microsomes, non-competitive inhibition of enzyme from detergent-treated microsomes
N-(pyridine-2-yl)morpholine-4-carbothioamide
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35.32% inhibition
N-(pyridine-2-yl)piperidine-4-carbothioamide
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38.88% inhibition
nicotinaldehyde dibenzylhydrazone
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oxaloacetate
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in complex with Mg2+, inhibition at low substrate concentrations, inhibition of the translocase component of the glucose 6-phosphatase system
p-hydroxy mercury-phenylsulfonate
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p-hydroxy mercurybenzoic acid
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palmitoyl-CoA
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inhibits enzyme activity in intact microsomes
Phenobarbital
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the inhibition in dependence on the age of rats is studied
phosphoinositides
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in order of decreasing efficiency: phosphatidylinositol, L-alpha-phosphatidylinositol 3,4,5-trisphosphate, L-alpha-phosphatidylinositol 3,4-diphosphate, alpha-phosphatidylinositol 4,5-diphosphate, alpha-phosphatidylinositol 3-monophosphate, alpha-phosphatidylinositol 4-monophosphate, phosphatidylinositol. Mechanism of inhibition with alpha-phosphatidylinositol 3,4-diphosphate, alpha-phosphatidylinositol 4,5-diphosphate or L-alpha-phosphatidylinositol 3,4,5-trisphosphate is competitive
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pyridine-2-carbaldehyde dibenzylhydrazone
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pyrocatechol-O-beta-D-glucopyranoside
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quercetin-3-O-beta-D-glucopyranoside
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S5627
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potent linear competitive inhibitor of the translocase component of the multicomponent hepatic glucose 6-phosphatase system
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silibinin
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induces a dose-dependent inhibition of gluconeogenesis associated with a potent decrease in enzyme activity; inhibits gluconeogenesis and D-glucose 6-phosphate hydrolysis from either lactate/pyruvate, glycerol or fructose in a dose-dependent manner. Effect is stronger in intact than in permeabilized microsomes
sodium barbital
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3 mM, complete inhibition
sodium pentobarbital
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3 mM, complete inhibition
Svetol
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commercial unroasted and decaffeinated green Coffea canephora extract, competive inhibition
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tetrahydrofuran-2-carbaldehyde dibenzylhydrazone
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tetrahydrothiophene-2-carbaldehyde dibenzylhydrazone
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tosyl-L-Lys-chloromethyl ketone
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inactivation of the enzyme in intact microsomes, no effect on enzyme in deoxycholate-modified microsomes
tosyl-L-Phe-chloromethyl ketone
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inactivation of the enzyme in intact microsomes, no effect on enzyme in deoxycholate-modified microsomes
tosyl-lysyl-chloromethane
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inhibitor of D-glucose 6-phosphate translocase
tosylphenylalanylchloromethane
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inhibitor of D-glucose 6-phosphate translocase
vanadyl acetylacetonate
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mixed-type inhibition
vanadyl sulfate
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37% inhibition at 0.048 microM, competitive inhibition
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4-methoxyphenyl-[4-(4-methoxyphenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl]methanone
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4-methoxyphenyl-[4-(4-methoxyphenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl]methanone
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4-methoxyphenyl-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl]methanone
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4-methoxyphenyl-[4-(4-trifluoromethoxyphenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl]methanone
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chlorogenic acid
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inhibitor of D-glucose 6-phosphate translocase
D-glucose
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non-competitive inhibitor, irrespective of the presence of detergents
D-glucose
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reduces the G6Pase activity both in intact and permeabilized liver microsomes in a concentration-dependent manner. Extent of inhibition is comparable with that achieved by epigallocatechin gallate in intact microsomes
molybdate
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phosphate
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phosphate
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non-competitive inhibition in intact microsomes, but competitive in the presence of detergents
S3483
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reversible inhibitor of the translocase component of the multicomponent hepatic glucose 6-phosphatase system
S3483
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only depresses G6Pase activity in intact microsomes, thus increases latency
vanadate
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vanadate
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reduces activity both in intact and permeabilized microsomes and decreases latency
additional information
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activity of glucose-6-phosphatase in crude microsomes from cells with high, normal, or low counting factor activity has a negative correlation with the amount of counting factor present in these cell lines. Molecules greater than 10 kDa from wild-type cells strongly repress activity of glucose-6-phosphatase in wild-type microsomes
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additional information
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The enzyme is inhibited by several amphiphilic compounds, such as fatty acids and acyl-CoAs, but the physioligal significance is questionable, since the liver contains a fatty-acyl CoA binding protein, which may well prevent this effect. Some thiol reagents inhibit enzyme activity much more in intact than in disrupted microsomes.
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additional information
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tumor necrosis factor inhibits the transcriptional rate of glucose-6-phosphatase in vivo and in vitro
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additional information
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insulin and epidermal growth factor inhibit basal mouse G6Pase fusion gene transcription
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additional information
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the effect of the short-chain aldehydes on the kinetic parameters increases with chain-length
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additional information
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a Pro metabolite inhibits glucose 6-phosphate hydrolysis and thus directs glucose 6-phosphate away from glucose production and towards glycogen
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additional information
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expression of dominant-negative versions of both cAMP response element-binding protein and CAAT/enhancer-binding protein blocks the glucose response of the proximal region in a dose-dependent manner
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additional information
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propyl gallate has no effect
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additional information
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a series of N,N-dibenzyl-N-benzylidnenhydrazine represent a novel class of potent competivitve D-glucose-6-phosphatase catalytic inhibitors using disrupted microsomes
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