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Glucose-Stimulated Genes and Prospects of Gene Therapy for Type I Diabetes¹

Institut Cochin de Génétique Moléculaire, Unité 129 de l’INSERM, Centre Hospitalo-Universitaire Cochin, 75014 Paris, France

I. Introduction

II. Transcriptional Regulation of Glucose-Responsive Genes

A. The insulin gene

1. Glucose-signaling pathway in pancreas ß-cells

2. E elements of the insulin gene promoter

3. A elements of the insulin gene promoter

4. Role of the E and A boxes of the insulin gene promoters in glucose-dependent transcriptional regulation

5. Role of the cAMP pathway in glucose responsiveness of the insulin gene promoters

B. Transcriptional regulation of glucose-responsive genes in the liver

1. The general outlook for glucose metabolism in the liver

2. Transcriptional glucose signaling mechanisms in the liver

3. Glucose/carbohydrate response elements

III. Cell and Gene Therapies for IDDM

A. Islet and cell transplantations

1. Transplantation of islets

2. Transplantation of established lines

B. Bioartificial pancreas

C. Transplantation of genetically engineered cells

1. The "ideal" engineered cell for glucose-dependent insulin secretion

2. Engineering established neuroendocrine cells

3. Engineering endogenous hepatocytes