Nitric oxide stimulates insulin release in liver cells expressing human insulin

Qingwen Qian, John P. Williams, Dennis G. Karounos, Sabire Özcan

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


The establishment of surrogate islet β cells is important for the treatment of diabetes. Hepatocytes have a similar glucose sensing system as β cells and have the potential to serve as surrogate β cells. In this report, we demonstrate that infection of Hepa1-6 liver cells with a lentivirus expressing the human insulin cDNA results in expression and secretion of human insulin. Furthermore, we show that l-arginine at low levels of glucose significantly stimulates the release of insulin from these cells, compared to exposure to high concentration of glucose. The arginine-induced insulin release is via the production of nitric oxide, since treatment with N G-nitro-l-arginine, an inhibitor of nitric oxide synthase, blocks insulin secretion induced by l-arginine. These results indicate that nitric oxide plays a role in l-arginine-stimulated insulin release in hepatocytes expressing the human insulin gene, and provides a new strategy to induce insulin secretion from engineered non-β cells.

Original languageEnglish
Pages (from-to)1329-1333
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - Apr 22 2005

Bibliographical note

Funding Information:
This work was supported by a grant from NIH (R21DK 0644829 to S.Ö.) and by UKRF and the Office of Research and Development, Medical Research Service, Department of Veterans Affairs (to D.G.K.). We thank Graeme Bell (University of Chicago) for the human insulin cDNA, Louis Hersh and the members of his laboratory for providing protocols on the lentivirus expression system, and Brett Spear for the Hepa1–6 cell line.


  • Arginine
  • Diabetes
  • Hepatocytes
  • Human insulin
  • Insulin secretion
  • Lentivirus
  • Nitric oxide
  • β cells

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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