Molecular mechanisms of alcohol associated pancreatitis

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.

ALDH1B1 links alcohol consumption and diabetes

“…Alcohol abuse is one of the major etiological factors for a variety of pancreatic disorders, including pancreatitis and diabetes [23, 24]. Numerous studies have demonstrated that ethanol and acetaldehyde exert deleterious effects on pancreatic exocrine and endocrine cells [25, 26].…”

Autophagy, Inflammation, and Immunity: A Troika Governing Cancer and Its Treatment

“…Another life threatening inflammatory disease associated with insufficient autophagy is chronic pancreatitis (Clemens et al, 2014). Chronic pancreatitis greatly increases pancreatic cancer risk and so do other pancreatitis and pancreatic cancer risk factors, such as alcohol consumption and high caloric intake, all of which interfere with autophagy activity (Clemens et al, 2014).…”

“…Chronic pancreatitis greatly increases pancreatic cancer risk and so do other pancreatitis and pancreatic cancer risk factors, such as alcohol consumption and high caloric intake, all of which interfere with autophagy activity (Clemens et al, 2014). Genetic manipulations that attenuate with autophagy lead to chronic pancreatitis in mice (Antonucci et al, 2015; Li et al, 2013).…”

Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation

“…However, approximately 20% of AP progresses to severe acute pancreatitis (SAP), a disease with high morbidity and mortality (Whitcomb, 2006; Clemens et al , 2014). AP is the most common gastrointestinal disease requiring hospitalization in the United States (Peery et al , 2012; Clemens et al , 2014). In 2009, there were 275,000 admissions for AP, accounting for a direct annual cost of $2.6 billion (Peery et al , 2012).…”