1. Susceptibility Factors and Cellular Mechanisms Underlying Alcoholic Pancreatitis
- Author
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Yi-Fan Miao, Subhankar Dolai, Fei Kang, Herbert Y. Gaisano, and Toshimasa Takahashi
- Subjects
Pancreatitis, Alcoholic ,Pancreatic stellate cell ,030508 substance abuse ,Medicine (miscellaneous) ,Hyperlipidemias ,Acetaldehyde ,Disease ,Infections ,Toxicology ,Bioinformatics ,Severity of Illness Index ,Exocytosis ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Autophagy ,medicine ,Humans ,Genetic Predisposition to Disease ,Obesity ,Receptor ,Ethanol ,business.industry ,Smoking ,Protective Factors ,Endoplasmic Reticulum Stress ,NAD ,medicine.disease ,Pathophysiology ,3. Good health ,Psychiatry and Mental health ,medicine.anatomical_structure ,Hepatic stellate cell ,Pancreatitis ,Calcium ,Disease Susceptibility ,Reactive Oxygen Species ,SNARE Proteins ,0305 other medical science ,business ,030217 neurology & neurosurgery - Abstract
Alcohol is a major cause of acute and chronic pancreatitis. There have been some recent advances in the understanding of the mechanisms underlying alcoholic pancreatitis, which include perturbation in mitochondrial function and autophagy and ectopic exocytosis, with some of these cellular events involving membrane fusion soluble N-ethylmaleimide-sensitive factor receptor protein receptor proteins. Although new insights have been unraveled recently, the precise mechanisms remain complex, and their finer details have yet to be established. The overall pathophysiology of pancreatitis involves not only the pancreatic acinar cells but also the stellate cells and duct cells. Why only some are more susceptible to pancreatitis and with increased severity, while others are not, would suggest that there may be undefined protective factors or mechanisms that enhance recovery and regeneration after injury. Furthermore, there are confounding influences of lifestyle factors such as smoking and diet, and genetic background. Whereas alcohol and smoking cessation and a generally healthy lifestyle are intuitively the advice given to these patients afflicted with alcoholic pancreatitis in order to reduce disease recurrence and progression, there is as yet no specific treatment. A more complete understanding of the pathogenesis of pancreatitis from which novel therapeutic targets could be identified will have a great impact, particularly with the stubbornly high fatality (>30%) of severe pancreatitis. This review focuses on the susceptibility factors and underlying cellular mechanisms of alcohol injury on the exocrine pancreas.
- Published
- 2020