Our preliminary studies in early weaned (15 d/o) neonatal rats showed the induction of proximal small intestinal and pancreatic ornithine decarboxylase (ODC) activities. The induction of ODC was 1-2 day earlier than the precocious expression of proximal showed for the first time the ontogeny of intestinal tyrosine kinases (Tyr-k) with parallelism between Tyr-k and growth and maturation of the rat small intestine. The overall aim of the current Grant Proposal is to define, at the cellular and gene expression level, the effect of early weaning on small intestinal and pancreatic development in neonatal rats. We will examine the role of these two proliferative enzymes-ODC and Tyr-K in the development of small intestine and pancreas after early weaning. Specifically we will: 1) Evaluate the growth and development parameters of small intestine and pancreas after early weaning and its relationship with ODC and Tyr-k. 2) Examine the essential roles of ODC and Tyr-K in the development of small intestine and pancreas after early weaning by administration of its respective inhibitor and assess the resultant effects of the development of these two organs. 3) Study (i) gene expression of ODC, Tyr-k (EGF-R Tyr-k and pp60c-src Tyr-k of small intestine, after early weaning. The findings from current proposed studies will enable us to understand the intracellular events and its regulatory mechanisms of developmental process of small intestine and pancreas in weaning and early weaning.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK002174-05
Application #
2749391
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Podskalny, Judith M
Project Start
1994-02-01
Project End
2002-07-31
Budget Start
1998-09-21
Budget End
2002-07-31
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Wayne State University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
Lin, Chuan-Hao; Vijesurier, Roy; Ho, Ye-Shih et al. (2002) Expression of intestinal ornithine decarboxylase during postnatal development in neonatal rats. Biochim Biophys Acta 1589:298-304
Lin, C H; Lyons, H; Seelbach, M S et al. (2001) Induction of gastric ornithine decarboxylase in early weaning rats. Digestion 63:214-9
Pillai, R B; Tolia, V; Rabah, R et al. (1999) Increased colonic ornithine decarboxylase activity in inflammatory bowel disease in children. Dig Dis Sci 44:1565-70
Lin, C H; Correia, L; Tolia, K et al. (1998) Early weaning induces jejunal ornithine decarboxylase and cell proliferation in neonatal rats. J Nutr 128:1636-42
Lin, C H; Moshier, J A; Luk, G D et al. (1997) Effect of thyroxine on pancreatic digestive enzymes and ornithine decarboxylase gene expression in neonatal rats. J Pediatr Gastroenterol Nutr 24:18-24