Adenoviral-mediated glucokinase overexpression in rat primary hepatocytes increases the efficiency of glycogen accumulation and lactate production at physiologic glucose concentrations

Journal Article

Glucokinase (GK) catalyses the conversion of glucose to glucose-6-phosphate, and is vital to the liver's role in maintaining glucose homeostasis. To address the effects of altered GK expression on liver carbohydrate metabolism, rat primary hepatocytes were treated with a recombmant adenovirus containing the cDNA of rat liver GK (AdCMVGKL+), and cultured in 1, 3, 5, 10, 15, or 25 mM glucose. GK activity in AdCMVGKL+ hepatocytes was 8.34±0.90-fold (p<0.01, n=9) higher than in controls (untreated hepatocytes, or hepatocytes treated with an adenoviral vector expressing β-galactosidase), and was unaffected by glucose culture conditions. Fold Increase of Glycogen and Lactate in AdCMVCKL+ Over Untreated Hepatocytes 1 3 5 10 15 25 (Glucose (mM)) Glycogen 1.1±0.2 1.7±0.1 4.6±10 18.1±4.1 25.3±3.6 1 5.7±1 .8 Lactae 3.0±0.2 4 9±0-5 5.1±0.3 6.5±0.3 4.7±0.3 3.7±0.2 Importantly, the levels of glycogen and lactate in AdCMVGKL+ hepatocytes cultured in 5mM glucose (230.0±50.0ug/mg protein and 14.94±0.98mM, respectively) were comparable to those observed in controls cultured in 25mM glucose (150.0±20.0ug/mg protein and 7.90±0.36mM, respectively), suggesting that increased glucose phosphorylation due to GK over expression increases the efficiency of glycogen synthesis and glycolysis at physiologic glucose concentrations.

Duke Authors

Cited Authors

  • O'Doherty, RM; Lehman, DL; Newgard, CB

Published Date

  • December 1, 1996

Published In

Volume / Issue

  • 10 / 3

International Standard Serial Number (ISSN)

  • 0892-6638

Citation Source

  • Scopus