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World J Gastrointest Pathophysiol. Aug 15, 2014; 5(3): 147-157
Published online Aug 15, 2014. doi: 10.4291/wjgp.v5.i3.147
Molecular mechanisms of alcohol associated pancreatitis
Dahn L Clemens, Mark A Wells, Katrina J Schneider, Shailender Singh
Dahn L Clemens, Nebraska-Western Iowa Veterans Administration Medical Center, Omaha, NE 68105, United States
Dahn L Clemens, Mark A Wells, Katrina J Schneider, Shailender Singh, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States
Dahn L Clemens, Shailender Singh, Fred and Pamela Buffett Cancer, University of Nebraska Medical Center, Omaha, NE 68198, United States
Author contributions: All the authors solely contributed to this paper.
Correspondence to: Dahn L Clemens, PhD, Department of Internal Medicine, University of Nebraska Medical Center, 4400 Emile St, Omaha, NE 68198, United States. dclemens@unmc.edu
Telephone: +1-402-9953738 Fax: +1-402-4490604
Received: March 21, 2014
Revised: April 26, 2014
Accepted: June 10, 2014
Published online: August 15, 2014
Abstract

Alcohol abuse is commonly associated with the development of both acute and chronic pancreatitis. Despite this close association, the fact that only a small percentage of human beings who abuse alcohol develop pancreatitis indicates that alcohol abuse alone is not sufficient to initiate clinical pancreatitis. This contention is further supported by the fact that administration of ethanol to experimental animals does not cause pancreatitis. Because of these findings, it is widely believed that ethanol sensitizes the pancreas to injury and additional factors trigger the development of overt pancreatitis. How ethanol sensitizes the pancreas to pancreatitis is not entirely known. Numerous studies have demonstrated that ethanol and its metabolites have a number of deleterious effects on acinar cells. Important acinar cells properties that are affected by ethanol include: calcium signaling, secretion of zymogens, autophagy, cellular regeneration, the unfolded protein response, and mitochondrial membrane integrity. In addition to the actions of ethanol on acinar cells, it is apparent that ethanol also affects pancreatic stellate cells. Pancreatic stellate cells have a critical role in normal tissue repair and the pathologic fibrotic response. Given that ethanol and its metabolites affect so many pancreatic functions, and that all of these effects occur simultaneously, it is likely that none of these effects is “THE” effect. Instead, it is most likely that the cumulative effect of ethanol on the pancreas predisposes the organ to pancreatitis. The focus of this article is to highlight some of the important mechanisms by which ethanol alters pancreatic functions and may predispose the pancreas to disease.

Keywords: Pancreatitis, Alcoholic pancreatitis, Alcoholic acute pancreatitis, Alcoholic chronic pancreatitis

Core tip: Alcohol abuse is commonly associated with the development of acute and chronic pancreatitis. Despite this close association, the fact that only a small percentage of human beings who abuse alcohol develop pancreatitis indicates that alcohol abuse alone is not sufficient to initiate clinical pancreatitis. It is widely believed that ethanol sensitizes the pancreas to injury and additional factors trigger the development of overt pancreatitis. How ethanol sensitizes the pancreas to pancreatitis in not entirely known. We will review the mechanisms by which ethanol is thought to sensitize human beings to pancreatic injury.