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

Regulated expression of human insulin in the liver of transgenic mice corrects diabetic alterations 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.—Valera, A., Fillat, C., Costa, C., Sabater, J., Visa, J., Pujol, A., Bosch, F. Regulated expression of human insulin in the liver of transgenic mice corrects diabetic alterations. FASEB J. 8: 440‐447; 1994. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The FASEB journal Wiley

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

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References (60)

Publisher
Wiley
Copyright
© Federation of American Societies for Experimental Biology
ISSN
0892-6638
eISSN
1530-6860
DOI
10.1096/fasebj.8.6.8168695
Publisher site
See Article on Publisher Site

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.—Valera, A., Fillat, C., Costa, C., Sabater, J., Visa, J., Pujol, A., Bosch, F. Regulated expression of human insulin in the liver of transgenic mice corrects diabetic alterations. FASEB J. 8: 440‐447; 1994.

Journal

The FASEB journalWiley

Published: Apr 1, 1994

Keywords: ; ; ; ;

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