Prolonged remission of diabetes by regeneration of beta cells in diabetic mice treated with recombinant adenoviral vector expressing glucagon-like peptide-1

Mol Ther. 2007 Jan;15(1):86-93. doi: 10.1038/


Type 1 diabetes results from insulin deficiency caused by destruction of pancreatic beta cells. Glucagon-like peptide (GLP)-1 stimulates beta cell growth and differentiation. To determine whether continuous expression of GLP-1 in vivo can regenerate beta cells and remit type 1 diabetes in mice for a prolonged time, we constructed an adenoviral vector containing the cytomegalovirus promoter/enhancer and albumin leader sequence followed by GLP-1 cDNA (rAd-GLP-1). A single administration of rAd-GLP-1 via the tail vein into streptozotocin (STZ)-induced diabetic non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice resulted in remission of diabetes within 10 days; normoglycemia remained until the experiment was terminated. The number of insulin-positive cells in the pancreas and insulin secretion significantly increased in rAd-GLP-1-treated mice compared with STZ-induced diabetic mice treated with rAd-beta-galactosidase. Glucose tolerance tests in mice that achieved normoglycemia after treatment with rAd-GLP-1 showed that the kinetics of glucose clearance was similar to normal NOD/SCID mice. Treatment of autoimmune diabetic mice with rAd-GLP-1 restored normoglycemia, which was maintained for 1 year when mice were also treated with an immunoregulator to halt the autoimmune response to beta cells. We suggest that regeneration of insulin-producing cells by GLP-1 gene therapy may be a potential method for prolonged control of type 1 diabetes in humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Cell Line
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / prevention & control*
  • Gene Expression / genetics*
  • Genetic Therapy
  • Genetic Vectors / genetics*
  • Glucagon-Like Peptide 1 / genetics
  • Glucagon-Like Peptide 1 / metabolism*
  • Humans
  • Immunohistochemistry
  • Insulin / blood
  • Insulin / genetics
  • Insulin-Secreting Cells / metabolism*
  • Mice
  • RNA, Messenger / genetics
  • Streptozocin / pharmacology


  • Insulin
  • RNA, Messenger
  • Streptozocin
  • Glucagon-Like Peptide 1