While in recent decades, considerable progress has been made in elucidating the cell biology of the exocrine pancreas, our knowledge of its pathophysiology as well as our ability to either prevent or treat pancreatitis remains very limited. This can be attributed in part to the relative inaccessibility to clinical material for experimental studies, which has necessitated the development of several models of experimental pancreatitis to explore its etiology, pathophysiology and treatment. The mouse is an ideal experimental animal in view of the availability of several genetic manipulations, accessibility to the complete mouse genome and the relatively lower cost and ease of maintenance, in fact, the most commonly used investigative model in experimental pancreatitis is that induced by caerulein in mice. However, caerulein only induces relatively mild form of the disease. While the CDE diet-induced model of pancreatitis does result in severe hemorrhagic pancreatitis that bears some resemblance to human disease, that model has several serious limitations restricting its usefulness. Clearly, there is a need to develop another mouse model of acute pancreatitis. We have been successful in inducing severe acute pancreatitis in mice by administration of arginine and the present proposal aims at characterizing this model extensively. The following four aims will be pursued to fully characterize this model: (1) To characterize dose, time and strain dependence of arginine-induced pancreatitis in mice; (2) To determine the mechanisms responsible for the onset of arginine-induced pancreatitis; (3) To elucidate the role of inflammatory mediators in the development and progression of arginine-induced acute pancreatitis in mice; and (4) Characterization of pancreatitis-associated lung injury. Successful completion of these studies will provide an excellent model of pancreatitis for future studies dealing with therapeutic interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
7R21DK072439-02
Application #
7140377
Study Section
Clinical and Integrative Gastrointestinal Pathobiology Study Section (CIGP)
Program Officer
Serrano, Jose
Project Start
2005-09-30
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2008-08-31
Support Year
2
Fiscal Year
2006
Total Cost
$182,484
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Surgery
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Dawra, Rajinder; Ku, Yang Sha; Sharif, Rifat et al. (2008) An improved method for extracting myeloperoxidase and determining its activity in the pancreas and lungs during pancreatitis. Pancreas 37:62-8
Saluja, Ashok; Dudeja, Vikas (2008) Heat shock proteins in pancreatic diseases. J Gastroenterol Hepatol 23 Suppl 1:S42-5
Dawra, Rajinder; Sharif, Rifat; Phillips, Phoebe et al. (2007) Development of a new mouse model of acute pancreatitis induced by administration of L-arginine. Am J Physiol Gastrointest Liver Physiol 292:G1009-18
Pandol, Stephen J; Saluja, Ashok K; Imrie, Clement W et al. (2007) Acute pancreatitis: bench to the bedside. Gastroenterology 132:1127-51