Hepatic insulin gene expression as treatment for type 1 diabetes mellitus in rats

Molecular Endocrinology
P MuzzinS L Woo

Abstract

Type 1 diabetes mellitus is caused by a lack of insulin that results from the autoimmune destruction of the pancreatic beta-cells. Severe diabetes, if not controlled by periodic insulin injections, can lead to ketoacidosis and death. We have previously shown that sustained low level production of insulin in the liver of diabetic rats prevented their death from complications of diabetes. To test the hypothesis that there is a window of serum insulin concentrations that can prevent ketoacidosis without significant risk of hypoglycemia secondary to hyperinsulinemia, rats were infused with various doses of a recombinant retrovirus encoding an engineered rat preproinsulin-1 gene. The gene was engineered to allow processing into mature insulin by the protease furin. At the lower doses tested, fatal ketoacidosis was prevented, but the rats exhibited nonfasting hyperglycemia. At intermediate doses, which resulted in serum insulin concentrations of 1.6 mg/ml, the rats achieved near-normoglycemia and no serum ketones. These rats did not exhibit hypoglycemia even during a 24-h fast. At high virus doses, the animals achieved nonfasting normoglycemia but exhibited hypoglycemia during the fast. In conclusion, we have defined a therapeutic wi...Continue Reading

References

Apr 11, 1995·Proceedings of the National Academy of Sciences of the United States of America·T M KolodkaS L Woo
Sep 1, 1993·Somatic Cell and Molecular Genetics·T M KolodkaS L Woo
Apr 1, 1994·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A ValeraF Bosch

❮ Previous
Next ❯

Citations

Aug 30, 2008·Expert Opinion on Drug Delivery·Darin E Olson, Peter M Thulé
Nov 26, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A W WolkoffB F Scharschmidt
May 6, 2003·The Journal of Gene Medicine·France Croze, Gérald J Prud'homme
Oct 2, 2004·Nature Reviews. Immunology·Yuti ChernajovskyOsvaldo L Podhajcer
Mar 1, 2000·Gene Therapy·P M ThuléL S Phillips
Nov 18, 2000·Gene Therapy·P M Thulé, J M Liu
Apr 9, 2015·Journal of Diabetes·Shen QuH Henry Dong
Feb 18, 2004·World Journal of Gastroenterology : WJG·Chen-Xia HeJing-Lun Xue
May 23, 2002·The Journal of Thoracic and Cardiovascular Surgery·Hitoshi SuharaHikaru Matsuda
Apr 26, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·R ChenS L Woo
Oct 11, 2003·Biochemical and Biophysical Research Communications·Kakei YasutomiOsam Mazda
Aug 29, 2021·Pharmaceutics·Nolwenn TessierCatherine Martel

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diabetes & Tolerance

Patients with type I diabetes lack insulin-producing beta cells due to the loss of immunological tolerance and autoimmune disease. Discover the latest research on targeting tolerance to prevent diabetes.