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Glucokinase overexpression restores glucose utilization and storage in cultured hepatocytes from male Zucker diabetic fatty rats.

Publication ,  Journal Article
Seoane, J; Barberà, A; Télémaque-Potts, S; Newgard, CB; Guinovart, JJ
Published in: J Biol Chem
November 5, 1999

Zucker diabetic fatty rats develop type 2 diabetes concomitantly with peripheral insulin resistance. Hepatocytes from these rats and their control lean counterparts have been cultured, and a number of key parameters of glucose metabolism have been determined. Glucokinase activity was 4.5-fold lower in hepatocytes from diabetic rats than in hepatocytes from healthy ones. In contrast, hexokinase activity was about 2-fold higher in hepatocytes from diabetic animals than in healthy ones. Glucose-6-phosphatase activity was not significantly different. Despite the altered ratios of glucokinase to hexokinase activity, intracellular glucose 6-phosphate concentrations were similar in the two types of cells when they where incubated with 1-25 mM glucose. However, glycogen levels and glycogen synthase activity ratio were lower in hepatocytes from diabetic animals. Total pyruvate kinase activity and its activity ratio as well as fructose 2,6-bisphosphate concentration and lactate production were also lower in cells from diabetic animals. All of these data indicate that glucose metabolism is clearly impaired in hepatocytes from Zucker diabetic fatty rats. Glucokinase overexpression using adenovirus restored glucose metabolism in diabetic hepatocytes. In glucokinase-overexpressing cells, glucose 6-phosphate levels increased. Moreover, glycogen deposition was greatly enhanced due to the activation of glycogen synthase. Pyruvate kinase was also activated, and fructose-2,6-bisphosphate concentration and lactate production were increased in glucokinase-overexpressing diabetic hepatocytes. Overexpression of hexokinase I did not increase glycogen deposition. In conclusion, hepatocytes from Zucker diabetic fatty rats showed depressed glycogen and glycolytic metabolism, but glucokinase overexpression improved their glucose utilization and storage.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

November 5, 1999

Volume

274

Issue

45

Start / End Page

31833 / 31838

Location

United States

Related Subject Headings

  • Rats, Zucker
  • Rats
  • Phosphorylation
  • Male
  • Liver Glycogen
  • Liver
  • Lactic Acid
  • Glycolysis
  • Glycogen Synthase
  • Glucose
 

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Seoane, J., Barberà, A., Télémaque-Potts, S., Newgard, C. B., & Guinovart, J. J. (1999). Glucokinase overexpression restores glucose utilization and storage in cultured hepatocytes from male Zucker diabetic fatty rats. J Biol Chem, 274(45), 31833–31838. https://doi.org/10.1074/jbc.274.45.31833
Seoane, J., A. Barberà, S. Télémaque-Potts, C. B. Newgard, and J. J. Guinovart. “Glucokinase overexpression restores glucose utilization and storage in cultured hepatocytes from male Zucker diabetic fatty rats.J Biol Chem 274, no. 45 (November 5, 1999): 31833–38. https://doi.org/10.1074/jbc.274.45.31833.
Seoane J, Barberà A, Télémaque-Potts S, Newgard CB, Guinovart JJ. Glucokinase overexpression restores glucose utilization and storage in cultured hepatocytes from male Zucker diabetic fatty rats. J Biol Chem. 1999 Nov 5;274(45):31833–8.
Seoane, J., et al. “Glucokinase overexpression restores glucose utilization and storage in cultured hepatocytes from male Zucker diabetic fatty rats.J Biol Chem, vol. 274, no. 45, Nov. 1999, pp. 31833–38. Pubmed, doi:10.1074/jbc.274.45.31833.
Seoane J, Barberà A, Télémaque-Potts S, Newgard CB, Guinovart JJ. Glucokinase overexpression restores glucose utilization and storage in cultured hepatocytes from male Zucker diabetic fatty rats. J Biol Chem. 1999 Nov 5;274(45):31833–31838.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

November 5, 1999

Volume

274

Issue

45

Start / End Page

31833 / 31838

Location

United States

Related Subject Headings

  • Rats, Zucker
  • Rats
  • Phosphorylation
  • Male
  • Liver Glycogen
  • Liver
  • Lactic Acid
  • Glycolysis
  • Glycogen Synthase
  • Glucose