Stimulation of glucose phosphorylation by fructose in isolated rat hepatocytes

Schaftingen, Emile Van; Vandercammen, Annick

doi:10.1111/j.1432-1033.1989.tb14537.x

Cited by 107 publications

(112 citation statements)

References 32 publications

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“…Fructose 1-phosphate has been shown to relieve the inhibition that a regulatory protein exerts on liver glucokinase in the presence of fructose 6-phosphate [18]. Because of this property, fructose 1-phosphate is thought to mediate the effect of fructose to stimulate 2-4-fold the phosphorylation of glucose [19].…”

Section: Discussionmentioning

confidence: 99%

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Presence of fructokinase in pancreatic islets

Malaisse¹,

Malaisse‐Lagae²,

Davies

et al. 1989

FEBS Letters

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Homogenates of rat pancreatic islets that had been heated for 5 min at 70°C to inactive hexokinases, catalyzed the ATPdependent phosphorylation of D-fructose. This reaction was dependent on the presence of K + and was inhibited by D-tagatose although not by D-glucose or D-glucose 6-phosphate. The phosphorylation product was identified as fructose 1-phosphate through its conversion to a bisphosphate ester by Clostridium difficile fructose l-phosphate kinase. These findings allowed the conclusion that fructokinase (ketohexokinase) was responsible for this process. Similar results were observed with tumoral insulin-producing ceils (R/Nm5F line). Fructokinas¢ may account for a large share of fructose phosphorylation in intact islets, particularly in the presence of D-glucose.Pancreatic islet; Fructokinase; (Ketohexokinase, Tumoral islet cell)

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Section: Discussionmentioning

confidence: 99%

“…Because of this property, fructose 1-phosphate is thought to mediate the effect of fructose to stimulate 2-4-fold the phosphorylation of glucose [19]. Since the islets also contain glucokinase [reviewed in 20] and are capable of synthesising fructose 1-phosphate, a similar mechanism could occur in that tissue [21].…”

Section: Discussionmentioning

confidence: 99%

Presence of fructokinase in pancreatic islets

Malaisse¹,

Malaisse‐Lagae²,

Davies

et al. 1989

FEBS Letters

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“…In rat liver fructose increases uptake and phosphorylation of glucose and its conversion to glycogen, lactate, CO2 and amino acids (reviewed in [54]). The mechanism of the fructose effect has been investigated by Dr. E. Van Schaftingen and his colleagues.…”

Section: Glucokinase Regulator Proteinmentioning

confidence: 99%

“…The mechanism of the fructose effect has been investigated by Dr. E. Van Schaftingen and his colleagues. In an outstanding series of papers [54][55][56][57][58][59] they show that hepatic GK is inhibited by fructose 6-phosphate (Ki 40 gmol/1 [59]), that the effect of fructose 6-phosphate is reversed by fructose 1-phosphate (K0.5 4.4 gmol/1), and that the effects of fructose phosphates require a specific regulatory protein [55]. In liver as in other tissues fructose 6-phosphate and glucose 6-phosphate are held in equilibrium by phosphoglucoisomerase.…”

Section: Glucokinase Regulator Proteinmentioning

confidence: 99%

Glucokinase and candidate genes for Type 2 (non-insulin-dependent) diabetes mellitus

Randle

1993

Diabetologia

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The fructose-6-phosphate-sensitive and fructose-I-phosphate-sensitive protein that inhibits rat liver glucokinase [Van Schaftingen, E. (1989) Eur. J .

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confidence: 99%

The mechanism by which rat liver glucokinase is inhibited by the regulatory protein

Vandercammen¹,

Schaftingen²

1990

European Journal of Biochemistry

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The fructose-6-phosphate-sensitive and fructose-I-phosphate-sensitive protein that inhibits rat liver glucokinase [Van Schaftingen, E. (1989) Eur. J . Bioclzern. 179, 179-1841 was purified close to homogeneity by a procedure involving poly(ethyleneglyco1) precipitation, chromatography on anion-exchangers and hydroxylapatite, gel filtration and chromatography on Mono S, a cation exchanger. In the last chromatographic step, the regulatory protein coeluted with a 62 kDa peptide. From the elution volume of the gel-filtration column a molecular mass of 60 kDa was determined, allowing the conclusion that the regulator is a monomer.The decrease in the apparent affinity of glucokinase for glucose, which the regulator induced, disappeared upon separation of the two proteins. Furthermore, the regulator did not appear to catalyse the formation of a heat-stable or a trypsin-resistant inhibitor of glucokinase. Finally, the inhibition exerted by the regulatory protein reached a steady value 1-2 min after the addition of the regulator. These results indicate that the regulator does not act by causing a covalent modification of glucokinase nor by catalysing the formation of a low-molecularmash inhibitor.Raising the concentration of glucokinase in the assay from 6 mU/ml to 120 mU/ml caused a 2.5-fold increase in the concentration of regulator required to half-maximally inhibit the enzyme. The apparent mass of glucokinase, as determined by centrifugation in isokinetic sucrose gradient, was 55 kDa, and this value was unaffected by the separate presence of fructose 6-phosphate or of the regulatory protein. However, the apparent mass of the enzyme increased to 105 kDa when glucokinase was centrifuged together with both fructose 6-phosphate and the regulatory protein, although not when fructose 1 -phosphate was also present. Conversely, the presence of glucokinase increased the apparent molecular mass of the regulator in the presence of fructose 6-phosphate. From these results, it is concluded that the regulatory protein inhibits glucokinase by forming a complex with this enzyme in the presence of fructose 6-phosphate, and that fructose 1-phosphate antagonises this inhibition by preventing the formation of the complex.Our laboratory has recently reported the occurrence in the liver of a regulatory protein which, in the presence of Fru6P, inhibits glucokinase competitively with respect to glucose [I]. This inhibition is antagonised by FrulP, which acts competitively with Fru6P. The properties of this protein allow one to account for the fact that fructose stimulates the phosphorylation of glucose in isolated rat hepatocytes [2].Several mechanisms could conceivably account for the action of the regulatory protein on glucokinase. The regulator could cause a covalent modification of the enzyme. It could also catalyse the formation of a low-molecular-mass inhibitor, possibly from Fru6P, since this compound greatly reinforces the inhibition exerted by the regulatory protein [I]. Finally the protein could inhibit glucokinase by forming a co...

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Stimulation of glucose phosphorylation by fructose in isolated rat hepatocytes

Cited by 107 publications

References 32 publications

Presence of fructokinase in pancreatic islets

Presence of fructokinase in pancreatic islets

Glucokinase and candidate genes for Type 2 (non-insulin-dependent) diabetes mellitus

The mechanism by which rat liver glucokinase is inhibited by the regulatory protein

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