Abstract

The goal of this project is to understand the mechanisms that underlie the development of the pancreatic islet of Langerhans into four distinct classes of cells, the alpha, beta, delta, and PP cells. Despite their common derivation and parallel development, the islet cell types are distinguished by their ability to express distinct gene products, especially the different islet peptide hormones. This project focuses on the intercellular and inter-islet regulatory networks that develop and maintain the differentiation islet cell phenotypes by regulating islet gene expression, and the potential role of these mechanisms in the pathogenesis of the two major forms of diabetes mellitus.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK041822-10
Application #
6105429
Study Section
Project Start
1998-08-10
Project End
2001-07-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
10
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Wilson, Maria E; Scheel, David; German, Michael S (2003) Gene expression cascades in pancreatic development. Mech Dev 120:65-80
Sander, M; Sussel, L; Conners, J et al. (2000) Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas. Development 127:5533-40
Shi, Y; Kanaani, J; Menard-Rose, V et al. (2000) Increased expression of GAD65 and GABA in pancreatic beta-cells impairs first-phase insulin secretion. Am J Physiol Endocrinol Metab 279:E684-94
Sander, M; Paydar, S; Ericson, J et al. (2000) Ventral neural patterning by Nkx homeobox genes: Nkx6.1 controls somatic motor neuron and ventral interneuron fates. Genes Dev 14:2134-9
Roll, U; Turck, C W; Gitelman, S E et al. (2000) Peptide mapping and characterisation of glycation patterns of the glima 38 antigen recognised by autoantibodies in Type I diabetic patients. Diabetologia 43:598-608
Smith, S B; Ee, H C; Conners, J R et al. (1999) Paired-homeodomain transcription factor PAX4 acts as a transcriptional repressor in early pancreatic development. Mol Cell Biol 19:8272-80
Kanaani, J; Lissin, D; Kash, S F et al. (1999) The hydrophilic isoform of glutamate decarboxylase, GAD67, is targeted to membranes and nerve terminals independent of dimerization with the hydrophobic membrane-anchored isoform, GAD65. J Biol Chem 274:37200-9
Schwartz, H L; Chandonia, J M; Kash, S F et al. (1999) High-resolution autoreactive epitope mapping and structural modeling of the 65 kDa form of human glutamic acid decarboxylase. J Mol Biol 287:983-99
Bridgett, M; Cetkovic-Cvrlje, M; O'Rourke, R et al. (1998) Differential protection in two transgenic lines of NOD/Lt mice hyperexpressing the autoantigen GAD65 in pancreatic beta-cells. Diabetes 47:1848-56
Damert, A; Machein, M; Breier, G et al. (1997) Up-regulation of vascular endothelial growth factor expression in a rat glioma is conferred by two distinct hypoxia-driven mechanisms. Cancer Res 57:3860-4

Showing the most recent 10 out of 27 publications