Gene therapy for diabetes: reinventing the islet.
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.
Samson
Susan L
SL
Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Chan
Lawrence
L
D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000628:therapy*; D015316:Genetic Therapy; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; C093970:NEUROD1 protein, human; C498695:NEUROG3 protein, human; C084010:pancreatic and duodenal homeobox 1 protein