The mechanisms responsible for generating alcohol-induced pancreatitis are largely unknown. This grant proposal requests support for a multi-disciplinary workshop that will discuss alcohol-induced injury with particular emphasis on the effect of this agent on the exocrine pancreas. Ethanol toxicity may be related to both its acute and chronic effects. Further, ethanol may be directly toxic, be metabolized to, or stimulate the generation of toxic agents. One of the important features of alcoholic pancreatitis is that few abusers develop the disease. This fact suggests that important genetic or environmental factors may influence the development of the disease. The importance of these factors in the pathogenesis of alcohol-induced pancreatitis remains unclear. However, important and potentially relevant observations have been made in other systems and particularly in studies of hepatic toxicity. These include studies of receptor function, vesicular trafficking, proteolysis, and cellular energy production in hepatocytes. Studies of ethanol-induced pancreatic disease have been hampered by the lack of a suitable experimental model. However, some progress has been made in developing suitable models. Further, studies of ethanol toxicity in experimental models have identified effects of the agent that may be relevant to human disease. The findings include enhanced proteolysis within the acinar cell in response to cholecystokinin and ethanol sensitization of rats in the cerulein model of pancreatitis. The non-oxidative ethanol metabolite, non-esterified free fatty acid, may also sensitize the pancreas to injurious stimulation.
The aims of the meeting are to bring together investigators interested in the toxic effects of ethanol in either the pancreas or other systems and present information that may be useful for studies of pancreatic diseases. Investigators in the pancreatic field will present cutting edge studies that include such topics as new models of ethanol-induced pancreatic damage and the effects of ethanol on gene transcription. The format of the meeting will be a combination of 30 min overviews, 15 min presentations of original data, and State of the Art Lectures. Young investigators will be invited to participate in the meeting and to present posters on this topic. Support for young investigators expenses will be sought from the American Gastroenterological Association Research Committee. The meeting Will last for one and a half days and immediately follow the annual meeting of the American Pancreatic Association in Chicago, IL, Nov. 5 to Nov. 7, 1999.
