Regulated expression of human insulin in the liver of transgenic mice corrects diabetic alterations

Alfons Valeka, Ckistina Fillat, Cristina Costa, Jordi Sabater, Joana Visa, Anna Pujol, Fatima Bosch

Research output: Contribution to journalArticleResearchpeer-review

60 Citations (Scopus)

Abstract

Transgenic mice expressing the P-enolpyruvate carboxykinase (PEPCK)/human insulin chimeric gene have been obtained as a model to study the feasibility of gene therapy for diabetes. These transgenic animals were healthy and normoglycemic and expressed human insulin in a physiologically regulated manner, mainly in the liver. Streptozotocin-treated transgenic mice had high levels of human insulin immunoreactivity in serum and showed a significant decrease (up to 40%) in glycemia compared with streptozotocin-treated control mice. The expression of genes involved in liver glucose metabolism, such as glucokinase, pyruvate kinase, and PEPCK, which is markedly altered by diabetes, was significantly recovered in transgenic mice treated with streptozotocin. In addition, the activity of both glucokinase and glycogen synthase, and the content of glucose 6-phosphate and glycogen, were normal in the liver, even when transgenic animals were treated with diabetogenic doses of streptozotocin. These results constitute an indication in vivo that diabetes gene therapy is possible, by means of the production of insulin in extrapancreatic tissues.
Original languageEnglish
Pages (from-to)440-447
JournalFASEB Journal
Volume8
Issue number6
Publication statusPublished - 27 May 1994

Keywords

  • diabetes
  • gene therapy
  • insulin
  • P-enolpyruvate carboxykinase
  • transgenic mice

Fingerprint Dive into the research topics of 'Regulated expression of human insulin in the liver of transgenic mice corrects diabetic alterations'. Together they form a unique fingerprint.

  • Cite this

    Valeka, A., Fillat, C., Costa, C., Sabater, J., Visa, J., Pujol, A., & Bosch, F. (1994). Regulated expression of human insulin in the liver of transgenic mice corrects diabetic alterations. FASEB Journal, 8(6), 440-447.