In this revised R29 application, we plan to characterize pancreatic reg I. Preliminary experiments have shown that reg I expression correlates with insulin gene expression, islet proliferation and even beta-cell function. The human protein is mitogenic to beta- and ductal cells, indicating that its mechanism of action is probably through induction of proliferation. A biologically active fragment has been isolated. Experiments in this grant are focused on the mechanism of rat reg I action.
Our Specific Aims are: (1) Isolate rat reg I protein and determine mitogenesis on pancreatic-derived cells. (2) Perform bindings studies of rat reg I protein with pancreatic target cells. (3) Determine whether pancreatic reg I is critical for normal islet function. Research design and methods: Rat reg I has been cloned into an expression vector and recombinant protein produced. Mitogenesis of the protein and the biologically active fragment to pancreatic-derived cells will be assayed by thymidine and BrdU incorporation. Binding studies to pancreatic target cells will be performed using radiolabelled protein. To characterize the role of reg I in beta-cell function, a rat model of acinar cell loss has been developed. Progressive loss of pancreatic reg I will be correlated with impaired glucose tolerance. Candidate: The candidate is a gastrointestinal surgeon interested in basic pancreatic physiology, and has proven ability as an independent investigator. Environment: Research will be carried out in the laboratory of the candidate. A formal collaboration has been established with the Diabetes Research and Training Center, which contains molecular, antibody and receptor analysis Research facilities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK054511-03
Application #
6164547
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Serrano, Jose
Project Start
1998-05-01
Project End
2001-02-28
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
3
Fiscal Year
2000
Total Cost
$168,000
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Surgery
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Viterbo, Domenico; Callender, Gordon E; DiMaio, Theresa et al. (2009) Administration of anti-Reg I and anti-PAPII antibodies worsens pancreatitis. JOP 10:15-23
Sanchez, Didier; Mueller, Cathy M; Zenilman, Michael E (2009) Pancreatic regenerating gene I and acinar cell differentiation: influence on cellular lineage. Pancreas 38:572-7
Mueller, Cathy M; Zhang, Hong; Zenilman, Michael E (2008) Pancreatic reg I binds MKP-1 and regulates cyclin D in pancreatic-derived cells. J Surg Res 150:137-43
Bluth, Martin; Mueller, Cathy M; Pierre, Joelle et al. (2008) Pancreatic regenerating protein I in chronic pancreatitis and aging: implications for new therapeutic approaches to diabetes. Pancreas 37:386-95
Bluth, Martin; Lin, Yin-Yao; Zhang, Hong et al. (2008) Use of gene expression profiles in cells of peripheral blood to identify new molecular markers of acute pancreatitis. Arch Surg 143:227-33;discussion 233-4
Kandil, Emad; Lin, Yin-Yao; Bluth, Martin-H et al. (2006) Dexamethasone mediates protection against acute pancreatitis via upregulation of pancreatitis-associated proteins. World J Gastroenterol 12:6806-11
Bluth, Martin H; Patel, Sameer A; Dieckgraefe, Brian K et al. (2006) Pancreatic regenerating protein (reg I) and reg I receptor mRNA are upregulated in rat pancreas after induction of acute pancreatitis. World J Gastroenterol 12:4511-6
Zhang, H; Kandil, E; Lin, Y-Y et al. (2004) Targeted inhibition of gene expression of pancreatitis-associated proteins exacerbates the severity of acute pancreatitis in rats. Scand J Gastroenterol 39:870-81
Sanchez, Didier; Gmyr, Valery; Kerr-Conte, Julie et al. (2004) Implication of Reg I in human pancreatic duct-like cells in vivo in the pathological pancreas and in vitro during exocrine dedifferentiation. Pancreas 29:14-21
Zhang, Hong; Patel, Sameer A; Kandil, Emad et al. (2003) Pancreatic elastase is proven to be a mannose-binding protein--implications for the systemic response to pancreatitis. Surgery 133:678-88

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