Abstract

The overall objective of this proposal is to determine the capacity of human fetal pancreatic tissue to generate functional endocrine tissue in vitro and in vivo. These studies may provide important information relevant to diabetes and islet cell physiology.
The specific aims are: 1. To study growth and development of human fetal islet cells and their precursors. a. Generation of islets or islet cell clusters (ICCs) and monolayers. b. Isolation of pure populations of islet cell precursors from ICCs and monolayers. (i) Cell sorting and beta-galactosidase (beta-gal) content. (ii) Infection with a retroviral vector containing the thymidine kinase (TK) gene. c. Expression of islet specific genes in whole pancreas, ICCs, and isolated islet cell populations. d. In vivo and in vitro functional studies using ICCs, monolayers and isolated islet cell populations. 2. To develop pancreatic beta-cell lines for studies of islet cell function in vitro and in vivo. a. Effects of the FGF family of growth factors on growth and differentiation of islet cells and their precursors. b. Development of an inducibly transformed pancreatic beta-cell line.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK039087-07
Application #
2140790
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1988-12-01
Project End
1995-11-30
Budget Start
1994-12-01
Budget End
1995-11-30
Support Year
7
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
University of California San Diego
Department
Pediatrics
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Beattie, G M; Lopez, A D; Otonkoski, T et al. (1999) Transplantation of human fetal pancreas: fresh vs. cultured fetal islets or ICCS. J Mol Med 77:70-3
Cirulli, V; Crisa, L; Beattie, G M et al. (1998) KSA antigen Ep-CAM mediates cell-cell adhesion of pancreatic epithelial cells: morphoregulatory roles in pancreatic islet development. J Cell Biol 140:1519-34
Wang, S; Beattie, G M; Mally, M I et al. (1997) Isolation and characterization of a cell line from the epithelial cells of the human fetal pancreas. Cell Transplant 6:59-67
Wang, S; Beattie, G M; Hayek, A et al. (1996) Development of a VSV-G protein pseudotyped retroviral vector system expressing dominant oncogenes from a lacO-modified inducible LTR promoter. Gene 182:145-50
Beattie, G M; Rubin, J S; Mally, M I et al. (1996) Regulation of proliferation and differentiation of human fetal pancreatic islet cells by extracellular matrix, hepatocyte growth factor, and cell-cell contact. Diabetes 45:1223-8
Otonkoski, T; Cirulli, V; Beattie, M et al. (1996) A role for hepatocyte growth factor/scatter factor in fetal mesenchyme-induced pancreatic beta-cell growth. Endocrinology 137:3131-9
Mally, M I; Cirulli, V; Hayek, A et al. (1996) ICA69 is expressed equally in the human endocrine and exocrine pancreas. Diabetologia 39:474-80
Itkin-Ansari, P; Bain, G; Beattie, G M et al. (1996) E2A gene products are not required for insulin gene expression. Endocrinology 137:3540-3
Mally, M I; Cirulli, V; Otonkoski, T et al. (1996) Ontogeny and tissue distribution of human GAD expression. Diabetes 45:496-501
Otonkoski, T; Hayek, A (1995) Constitution of a biphasic insulin response to glucose in human fetal pancreatic beta-cells with glucagon-like peptide 1. J Clin Endocrinol Metab 80:3779-83

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