Glucose-Stimulated Genes and Prospects of Gene Therapy for Type I Diabetes1
Delphine Mitanchez,
Bruno Doiron,
Ruihuan Chen and
Axel Kahn
Institut Cochin de Génétique Moléculaire,
Unité 129 de l’INSERM, Centre Hospitalo-Universitaire Cochin,
75014 Paris, France
I. Introduction
II. Transcriptional Regulation of Glucose-ResponsiveGenes
A. The insulin gene
1. Glucose-signaling pathway inpancreas ß-cells
2. E elements of the insulin gene promoter
3. A elements of the insulin gene promoter
4. Role of theE and A boxes of the insulin gene promoters in
glucose-dependenttranscriptional regulation
5. Role of the cAMP pathway inglucose responsiveness of theinsulin gene
promoters
B. Transcriptionalregulation of glucose-responsive genes inthe liver
1. Thegeneral outlook for glucose metabolism in the liver
2. Transcriptionalglucose signaling mechanisms in the liver
3. Glucose/carbohydrateresponse elements
III. Cell and Gene Therapies for IDDM
A.Islet and cell transplantations
1. Transplantation of islets
2. Transplantation of established lines
B. Bioartificialpancreas
C. Transplantation of genetically engineered cells
1. The "ideal" engineered cell for glucose-dependent insulinsecretion
2. Engineering established neuroendocrine cells
3. Engineering endogenous hepatocytes
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