Gene therapy for diabetes: reinventing the islet

Trends Endocrinol Metab. 2006 Apr;17(3):92-100. doi: 10.1016/j.tem.2006.02.002. Epub 2006 Feb 28.


A cure for type 1 (insulin dependent) diabetes might be found in generating surrogate insulin-producing cells to replace beta cells. A gene therapy strategy using constructs designed to allow glucose-regulated insulin transcription when delivered to non-pancreatic tissues has not fully recreated the stringent control of blood glucose provided by the beta cell. A more promising gene therapy approach has been to express pancreatic endocrine developmental factors, such as PDX-1, NeuroD/BETA2 and Neurogenin 3, to promote differentiation of non-endocrine cells towards a beta cell or islet phenotype, enabling these cells to synthesize and secrete insulin in a glucose-regulated manner. Further research is necessary, however, to better define the most effective pro-endocrine factors and the most amenable cell types to achieve transdifferentiation for beta cell replacement.

Publication types

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

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / therapy*
  • Genetic Therapy*
  • Homeodomain Proteins / genetics
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / metabolism*
  • Nerve Tissue Proteins / genetics
  • Trans-Activators / genetics


  • Basic Helix-Loop-Helix Transcription Factors
  • Homeodomain Proteins
  • Insulin
  • NEUROD1 protein, human
  • NEUROG3 protein, human
  • Nerve Tissue Proteins
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein