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Overexpression of hexokinase I in isolated islets of Langerhans via recombinant adenovirus. Enhancement of glucose metabolism and insulin secretion at basal but not stimulatory glucose levels.

Publication ,  Journal Article
Becker, TC; BeltrandelRio, H; Noel, RJ; Johnson, JH; Newgard, CB
Published in: J Biol Chem
August 19, 1994

Glucose metabolism and glucose-stimulated insulin secretion are thought to be controlled at the level of glucose phosphorylation in pancreatic islet beta-cells. In the current study we have investigated the importance of glucose phosphorylation by using recombinant adenovirus as a gene delivery system for isolated rat islets. Treatment of islets with a virus containing the cDNA encoding the Escherichia coli beta-galactosidase gene (AdCMV-beta GAL) resulted in efficiencies of gene transfer of 70.3 +/- 2.5 and 61.2 +/- 2.2% in two independent experiments. Treatment of islets with a virus containing the cDNA encoding rat hexokinase I (AdCMV-HKI) resulted in a 10.7-fold increase in immunodetectable hexokinase protein and a similar increase in enzyme activity. A large percentage of the overexpressed hexokinase activity was associated with a cell fraction enriched in mitochondria. These changes in enzyme level were accompanied by a 2-fold increase in insulin release and [5-3H]glucose usage at basal glucose concentrations (3 mM). The rate of glucose usage at 20 mM glucose and the magnitude of the insulin secretory response to this stimulatory level of the sugar were unchanged relative to control islets. Overexpression of hexokinase I in isolated islets therefore creates a phenotype of elevated basal insulin release similar to that seen in islets from obese and insulin-resistant mammals. The discrepancy between the large increase in hexokinase activity and the small increase in glucose usage and insulin release may indicate, however, that other steps in glucose metabolism become rate-limiting after only modest increases in glucose-phosphorylating activity.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

August 19, 1994

Volume

269

Issue

33

Start / End Page

21234 / 21238

Location

United States

Related Subject Headings

  • Recombination, Genetic
  • Rats, Wistar
  • Rats
  • Male
  • Islets of Langerhans
  • Insulin Secretion
  • Insulin
  • Hexokinase
  • Glucose
  • Escherichia coli
 

Citation

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Becker, T. C., H. BeltrandelRio, R. J. Noel, J. H. Johnson, and C. B. Newgard. “Overexpression of hexokinase I in isolated islets of Langerhans via recombinant adenovirus. Enhancement of glucose metabolism and insulin secretion at basal but not stimulatory glucose levels.J Biol Chem 269, no. 33 (August 19, 1994): 21234–38.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

August 19, 1994

Volume

269

Issue

33

Start / End Page

21234 / 21238

Location

United States

Related Subject Headings

  • Recombination, Genetic
  • Rats, Wistar
  • Rats
  • Male
  • Islets of Langerhans
  • Insulin Secretion
  • Insulin
  • Hexokinase
  • Glucose
  • Escherichia coli