Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 + 2751 word(s) 2751 2022-01-10 10:06:54 |
2 format correct Meta information modification 2751 2022-01-17 02:07:04 |

Video Upload Options

Do you have a full video?

Confirm

Are you sure to Delete?
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Luo, J. Alcohol Consumption and Pancreatitis. Encyclopedia. Available online: https://encyclopedia.pub/entry/18278 (accessed on 13 July 2024).
Luo J. Alcohol Consumption and Pancreatitis. Encyclopedia. Available at: https://encyclopedia.pub/entry/18278. Accessed July 13, 2024.
Luo, Jia. "Alcohol Consumption and Pancreatitis" Encyclopedia, https://encyclopedia.pub/entry/18278 (accessed July 13, 2024).
Luo, J. (2022, January 14). Alcohol Consumption and Pancreatitis. In Encyclopedia. https://encyclopedia.pub/entry/18278
Luo, Jia. "Alcohol Consumption and Pancreatitis." Encyclopedia. Web. 14 January, 2022.
Alcohol Consumption and Pancreatitis
Edit

Pancreatitis is a common inflammatory disorder of the pancreas, associated with high mortality and healthcare burdens worldwide. It mainly consists of two forms: acute pancreatitis (AP) and chronic pancreatitis (CP). Alcohol exposure is a known etiological factor for both AP and CP.

alcohol abuse endoplasmic reticulum stress unfolded protein response pancreatitis

1. Acute and Chronic Pancreatitis

Pancreatitis is a common inflammatory disorder of the pancreas, associated with high mortality and healthcare burdens worldwide [1][2]. It mainly consists of two forms: acute pancreatitis (AP) and chronic pancreatitis (CP). AP is the most frequent cause of gastrointestinal disorders requiring hospitalization in the US, and its associated inpatient care cost is approximately USD 2.6 billion annually [2][3][4]. Although less frequent, CP also causes significant morbidity and financial burden [3]. Additionally, the incidence of pancreatitis differs with age and gender. The risk of developing AP increases with age [5][6], whereas CP is more common in middle-aged individuals [2]. Furthermore, AP does not appear to differ between men and women [6]; however, CP is more common in men than in women [2][7]. AP and CP share a significant portion of clinical manifestations and phenotypes, but also have distinct morphological and imaging features.
AP is characterized by sudden abdominal pain, elevated levels of pancreatic enzymes in the blood, and pancreatic inflammation [8][9]. Depending on the clinical features, AP can be classified into mild, moderate, or severe forms. The most common form of AP is mild AP, which can be self-treated within weeks. However, the moderate and severe forms can progress into necrotizing pancreatitis, which has a 20–40% mortality rate [10]. A variety of long-term sequelae have been reported that can persist beyond hospital admission for AP. AP may increase the risk of other pancreatic disorders, including CP, exocrine pancreatic insufficiency (EPI), pancreatic cancer (PC) and diabetes mellitus (DM). In total, 17% of AP patients are re-admitted after their first episode for recurrent pancreatitis with about 8% of patients developing CP [11][12]. Approximately one quarter to one third of AP patients develop EPI during the follow-up period [13][14]. The prevalence of EPI following AP is higher with the severe form than with the mild form, and it is higher in patients with an etiology of alcohol than one of gallstones [14]. AP patients often develop prediabetes and/or DM after being discharged from the hospital [15][16]. The diagnosis of AP increases the risk of PC, which in turn increases the number of recurrent episodes of AP [17][18].
CP is believed to result from the recurrence of AP, leading to chronic pain, pancreatic atrophy, duct strictures and calcifications [19][20]. Although less common than AP, CP significantly affects patients’ quality of life due to irreversible, debilitating injury to the function of the pancreas. CP is also associated with other pancreatic diseases. It has been reported that CP increases the risk of EPI [21][22], PC [23][24] and DM [25][26]. The high disease burden of AP and CP emphasizes the importance of identifying predisposing factors, understanding pathogenesis, and developing therapeutic intervention for these diseases.

2. Alcohol Consumption and Pancreatitis

Alcohol exposure is a known etiological factor for both AP and CP. Epidemiological studies have shown that excessive alcohol consumption is the second leading cause of AP after gallstones [1][27] and is the most prevalent risk factor for CP [28]. Alcohol abuse is also a risk factor for the recurrence of AP and increases the chance of the progression of AP into CP [11][29]. Although alcohol can contribute to the initiation and progression of pancreatitis, only a small number of heavy alcohol drinkers develop the disease, suggesting that other disposing factors are involved in the development of alcohol-related pancreatitis [7][30][31][32].
The association between alcohol consumption and pancreatitis is evaluated predominantly by self-reported survey studies. Corrao et al. conducted a meta-analysis of studies published from 1966 to 1995 and showed that the risk of pancreatitis monotonically increased with increasing alcohol consumption [33]. Consistent with this finding, Irving et al. analyzed research published from 1980 to 2008 and confirmed a monotonic dose–response relationship between alcohol consumption and the risk of pancreatitis, with a threshold of four drinks daily that significantly increased the risk of pancreatitis [34]. Similarly, more recent studies indicated that prolonged use of alcohol with a threshold level of 4–5 drinks per day was required for an increased risk of pancreatitis [19][31][34][35][36]. In addition, the amount of recently consumed alcohol was shown to determine the severity of the first episode of acute alcoholic pancreatitis [37]. In the absence of long-term use, binge drinking alone did not increase the incidence of AP [38]. Regular consumption of alcohol at lower levels, however, appeared to have an inconsistent effect on pancreatitis. Some reported that low levels of alcohol drinking (<50 g per day) increased the recurrence of AP and accelerated the progression of CP [39][40]. Others found that mild or moderate drinking was inversely associated with an increased risk of pancreatitis [41].
In contrast to prolonged heavy alcohol consumption, which has been known as a risk factor for pancreatitis, alcohol abstinence has been shown to slow down the progression of pancreatitis and reduce the recurrence of AP. For example, withholding from drinking resolved abdominal pain and slowed the deterioration of pancreatic function in chronic heavy drinkers [42]. Abstinence after the first episode of AP minimized the number of recurrent attacks [43]. Similarly, in an effort to determine the risk factors associated with recurrent pancreatitis, Pelli et al. (2008) showed that abstinence from alcohol protected against the recurrence of AP [44].
Alcohol can also act as a co-factor to increase the sensitivity of the pancreas to the detrimental effect of other risk factors, including environmental and dietary factors [45]. Cigarette smoking is an independent risk factor for a number of pancreatic disorders, including AP [46], CP [47] and PC [48][49]. Alcohol drinking can accelerate the progression of cigarette-smoking-related pancreatitis and vice versa, suggesting a synergistic interaction between alcohol and smoking in the development of the disease [36][50][51][52]. Hypertriglyceridemia, referring to an elevated blood level of triglycerides often resulting from high dietary fats, is another important cause for pancreatitis [53][54][55] and is present in many alcoholics [56][57]. Excessive alcohol consumption has been suggested to be associated with hypertriglyceridemia-induced pancreatitis [58][59].
The risk of alcoholic pancreatitis can also be altered by genetic modifiers. The CLDN2 (Clauding 2) gene encodes a tight junction protein-regulating cation and water transport of epithelial cells. It is normally expressed in pancreatic duct cells but not acinar cells [60][61]. In a genome-wide study, a CLDN2 risk allele, which is associated with an abnormal expression of CLDN2 protein in pancreatic acinar cells, was identified as a risk factor that interacted with alcohol consumption to accelerate the progression of chronic pancreatitis [62]. In another genome-wide association study, an inversion of the CTRB1–CTRB2 (chymotrypsin B1 and B2) locus led to both the imbalanced expression of CTRB1 and CTRB2 and an increased risk for both alcoholic CP and non-alcoholic CP [63].
Racial/ethnic differences are another susceptibility factor that can alter the risk of alcoholic pancreatitis. A population study using nationwide inpatient samples from the racially diverse US population between 1988 and 2004 demonstrated that Black people had the highest frequency of alcohol-related pancreatitis [64]. Another study using data collected by the North American Pancreatitis Study Group from 2000 to 2014 found that Black people were more likely to be diagnosed with CP than White people, likely because of alcohol consumption and smoking being more frequent in Black people [65]. In a number of studies conducted in the Asian population, a dose–response relationship between alcohol and pancreatitis was revealed [66][67][68]. The impact of ethnicity on the risk of alcoholic pancreatitis in these Asian studies was suggested to be related to the genetic polymorphism of alcohol metabolism enzymes. Genetic variant alleles of the aldehyde dehydrogenase-2 gene (ALDH2*2) and alcohol dehydrogenase-1B gene (ADH1B*2), which are associated with the accumulation of toxic acetaldehyde after alcohol drinking, were predominantly found in East Asians [69][70][71].

3. Animal and Cell Culture Models for Alcoholic Pancreatitis

Epidemiologic studies have indicated that alcohol can act as a mild initiator or a robust modifier that sensitizes the pancreas to the insult of other risk factors during the development of pancreatitis. To understand the mechanisms underlying the pathogenesis of alcohol-related pancreatitis, many animal and cell culture models have been established. These experimental models have recapitulated the clinical features of alcohol-related pancreatitis, facilitated our understanding of the pathology, and provided opportunities to test potential therapeutic treatments for the disease.
Consistent with epidemiologic studies, alcohol alone, either by acute exposure (77) or by chronic feeding [72][73][74], is not sufficient in inducing pancreatitis-like features in rodent models. Recent studies have combined chronic exposure with binge drinking and found that alcohol, when acting as both the initiation and susceptibility factor, can cause pancreatic injury, mimicking pancreatitis. Binge alcohol exposure by intragastric intubation for 10 consecutive days (5 g/kg/day, 25% ethanol w/v) caused pancreatic edema, acinar cell death and moderate fibrosis in C57BL mice [75]. Mice receiving a liquid alcohol diet for two weeks followed by binge alcohol exposure by oral gavage for 3 days (5 g/kg/day, 25% ethanol w/v) displayed more severe injury and inflammation in the pancreas [76]. A 10-day feeding of a liquid alcohol diet plus a single binge ethanol exposure was found to lead to pancreatic edema and inflammation in C57Bl/6 mice [77][78]. The chronic plus binge model may be of clinical relevance due to the similarity of the drinking pattern to that of many alcoholic patients who have a history of chronic alcohol consumption and tend towards heavy episodic drinking [79][80][81]. In fact, the chronic plus binge exposure has also been used in animal models for alcoholic liver disease (ALD), as it causes significantly higher elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and hepatic histological features, compared with chronic alcohol feeding or binge exposure alone [77][82][83].
The detrimental effects of alcohol on the pancreas can result from the direct actions of toxic metabolites, acetaldehyde and fatty acid ethyl esters (FAEEs), via the oxidative and non-oxidative pathways, respectively. The oxidative metabolism of ethanol mainly occurs in the liver [84][85][86] and the level of acetaldehyde in the circulation is typically low [87][88], meaning organ damage in the pancreas by acetaldehyde is considered insignificant. In contrast, non-oxidative metabolism of ethanol by esterification with fatty acids, resulting in the formation of FAEEs, has been implicated in alcohol-induced damage to the pancreas. An autopsy study showed that the level of FAEEs and the activity of FAEEs synthase (enzymes responsible for the synthesis of FAEEs) are highest in the pancreas among all ethanol-damaged organs in acutely intoxicated individuals [89]. In fact, intra-arteria infusion of FAEEs in rats at concentrations comparable to those in human plasma only caused AP-like injury in the pancreas but not in other organs that are known to be susceptible to ethanol-induced damage, implying a role of FAEEs as a mediator in ethanol-induced pancreas-specific toxicity [90]. In a ethanol-induced AP rat model, the inhibition of oxidative ethanol metabolism increased FAEEs concentration in the plasma and pancreas and exacerbated pancreatitis-like injury, suggesting FAEEs are responsible for pancreatic damage in alcohol-related AP [91]. With in vitro and in vivo models for AP induced by low ethanol and fat, Huang et al. (2014) showed that 3-benzyl-6-chloro-2-pyrone (3-BCP), an inhibitor of carboxylester lipase (a FAEE synthase produced by pancreatic acinar cells), reduced FAEEs formation and alleviated exocrine pancreatic damage, demonstrating a crucial role of FAEEs in alcohol-related AP [92].
Alcohol can also act as a co-factor to sensitize the pancreas to the adverse effects of other susceptibility factors in the progression of pancreatitis. One physiologically relevant animal model for alcohol-related pancreatitis is the co-exposure of cholecystokinin (CCK) analogs and alcohol. CCK, an intestine hormone, is one of the most commonly used models to induce mild AP in rats [93][94][95][96] and a more severe form in mice [97][98][99][100], with a dose that is at least 10 times higher than physiological conditions. CCK analog-induced AP can recapitulate the pathologic features of human AP caused by scorpion venom and cholinergic toxins [101][102][103][104]. The co-treatment of alcohol can either reduce the threshold concentration of CCK analogs required to elicit a pancreatitis response or intensify the pathologic response of the pancreas. Pandol et al. (1999) demonstrated that alcohol exposure sensitized rats to pancreatitis induced by CCK-8 at physiological concentration, which by itself did not cause pancreatitis [95]. Quon et al. (1992) showed that chronic feeding with an alcohol diet exacerbated CCK analog caerulein-induced pancreatitis in rats, signified by greater increases in serum lipase level, interstitial edema and acinar vacuolization compared with animals treated with caerulein alone [105]. Repeated use of caerulein over time induced pathological features of the pancreas in rodents that mimicked human CP [106][107][108]. Alcohol exposure accelerated the progression of caerulein-induced CP in rats [108] and mice [109].
Another clinically relevant animal model is lipopolysaccharides (LPS)-induced alcoholic pancreatitis in rodents [110]. LPS are endotoxins derived from Gram-negative bacteria in the gut, which can be released to the blood to cause LPS-associated toxicity [111]. There have been reports of higher plasma levels of LPS in alcoholics [112][113] and an association between plasma endotoxin concentrations and the severity of human AP [114]. In rat models, LPS and alcohol exposure have been shown to cause a more severe pancreatic injury than LPS alone [110][115]. Withdrawal of alcohol after manifestation of LPS-induced pancreatitis in rats resulted in the resolution of pancreatic lesions, including fibrosis and cell death, whereas continued alcohol administration aggravated the injury [116]. In a rat model of alcoholic AP, alcohol increased the expression of LPS-induced proinflammatory factors in acinar cells, including TNFα, IL-6, IL-10 and IL-18 [117]. The elevated expression of these inflammatory mediators was also observed in human AP and recurrent AP patient samples, suggesting an involvement of inflammation in alcoholic pancreatitis [117].
There are other susceptibility factors that have been identified in experimental models and shown to be associated with alcoholic pancreatitis. Pancreatic duct obstruction, which causes minimal pancreatic damage independently, induced pancreatitis in a rat model when combined with alcohol feeding [118] and worsened the canine model of alcoholic CP [119]. Genetic mutations, as exemplified by a pathogenic human p.N256K CPA1 (Carboxypeptidase A1) mutant when expressed in mice, caused protein misfolding, ER stress and progressive CP, which was aggravated by alcohol exposure [120]. A severe pancreatitis phenotype manifested in knock-out mice for nuclear factor erythroid 2 like 2 (NRF2), a regulator of cellular antioxidant response and ethanol metabolism, was worsened by acute binge alcohol exposure, suggesting the involvement of oxidative stress or ethanol metabolites in alcoholic pancreatitis [121].
In addition to animal models, many in vitro models have been proposed to address the mechanisms underlying the pathology of alcoholic pancreatitis. The exocrine compartment of the pancreas is mainly composed of acinar and ductal cells. The pancreatic acinar cells are the functional unit of the exocrine pancreas, constituting about 80% of the pancreas. Their function is to synthesize, store and secrete digestive enzymes. Acinar cells are believed by many to be the initiation site of pancreatic injury, as molecular and cellular events linked to acinar cell dysfunction have been shown to occur early in pancreatitis [122][123][124][125]. Similar to animal models, pancreatic acinar cells, when treated by alcohol alone, appeared to display minimal damages. Chronic alcohol exposure at a clinically relevant concentration (50 mM equivalent to 230 mg/dL, 96 h) reduced the cellular uptake of thiamine pyrophosphate (TPP) in rat primary acini, rat pancreatic AR42J acinar cells [126] and mouse pancreatic 266-6 acinar cells [127], indicative of alcohol’s damaging effects on pancreatic thiamine-dependent functions [128][129][130]. Alcohol exposure at concentrations from 200 to 800 mg/dL for 6 h caused mild apoptosis of AR42J cells and minimal effect on the activity of lipase or amylase [131]. Lugea et al. (2017) showed that alcohol treatment (50 mM equivalent to 230 mg/dL) for 4 days decreased the viability of AR42J cells only in combination with cigarette smoke extracts but not independently [132]. In CCK-8-stimulated primary mouse pancreatic acini, alcohol treatment altered Ca2+ homeostasis [133], increased reactive oxygen species (ROS) production [134] and reduced CCK-8-evoked amylase secretion [135]. In rat pancreatic acini, alcohol treatment exacerbated the pathological intra-acinar protease activation induced by muscarinic agonist carbachol [136].
Pancreatic ductal cells, which are responsible for transporting the acini-produced digestive enzymes into the duodenum and secreting bicarbonate-rich fluid to neutralize stomach acid, have also been proposed to be involved in the pathology of pancreatitis [137][138][139]. Alteration of ductal cell function may cause insufficient transportation or precipitation of digestive enzymes in the ducal lumen, potentially leading to obstruction and damage. Sarles et al. (1965) showed that the formation of mucoprotein plugs in the pancreatic ducts was an early lesion in the pathology of alcohol-induced chronic calcifying pancreatitis [140]. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an ion channel protein highly expressed in pancreatic duct cells, were found to be associated with CP [141]. Maleth et al. (2015) showed ethanol exposure reduced the expression of CFTR and disrupted the folding of CFTR at the endoplasmic reticulum (ER) in a number of human pancreatic cell lines and the pancreatic tissues of mice and guinea pigs [142]. In addition, CFTR knockout mice developed more severe pancreatitis when given ethanol than WT control mice [142].

References

  1. Lankisch, P.G.; Apte, M.; Banks, P.A. Acute pancreatitis. Lancet 2015, 386, 85–96.
  2. Yadav, D.; Lowenfels, A.B. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology 2013, 144, 1252–1261.
  3. Xiao, A.Y.; Tan, M.L.; Wu, L.M.; Asrani, V.M.; Windsor, J.A.; Yadav, D.; Petrov, M.S. Global incidence and mortality of pancreatic diseases: A systematic review, meta-analysis, and meta-regression of population-based cohort studies. Lancet Gastroenterol. Hepatol. 2016, 1, 45–55.
  4. Peery, A.F.; Dellon, E.S.; Lund, J.; Crockett, S.D.; McGowan, C.E.; Bulsiewicz, W.J.; Gangarosa, L.M.; Thiny, M.T.; Stizenberg, K.; Morgan, D.R.; et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology 2012, 143, 1179–1187.e1173.
  5. Yadav, D.; Lowenfels, A.B. Trends in the epidemiology of the first attack of acute pancreatitis: A systematic review. Pancreas 2006, 33, 323–330.
  6. Weiss, F.U.; Laemmerhirt, F.; Lerch, M.M. Etiology and Risk Factors of Acute and Chronic Pancreatitis. Visc. Med. 2019, 35, 73–81.
  7. Lankisch, P.G.; Lowenfels, A.B.; Maisonneuve, P. What is the risk of alcoholic pancreatitis in heavy drinkers? Pancreas 2002, 25, 411–412.
  8. Boxhoorn, L.; Voermans, R.P.; Bouwense, S.A.; Bruno, M.J.; Verdonk, R.C.; Boermeester, M.A.; van Santvoort, H.C.; Besselink, M.G. Acute pancreatitis. Lancet 2020, 396, 726–734.
  9. Banks, P.A.; Bollen, T.L.; Dervenis, C.; Gooszen, H.G.; Johnson, C.D.; Sarr, M.G.; Tsiotos, G.G.; Vege, S.S. Classification of acute pancreatitis—2012: Revision of the Atlanta classification and definitions by international consensus. Gut 2013, 62, 102–111.
  10. Bugiantella, W.; Rondelli, F.; Boni, M.; Stella, P.; Polistena, A.; Sanguinetti, A.; Avenia, N. Necrotizing pancreatitis: A review of the interventions. Int. J. Surg. 2016, 28 (Suppl. 1), S163–S171.
  11. Ahmed Ali, U.; Issa, Y.; Hagenaars, J.C.; Bakker, O.J.; van Goor, H.; Nieuwenhuijs, V.B.; Bollen, T.L.; van Ramshorst, B.; Witteman, B.J.; Brink, M.A.; et al. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis. Clin. Gastroenterol. Hepatol. 2016, 14, 738–746.
  12. Vipperla, K.; Papachristou, G.I.; Easler, J.; Muddana, V.; Slivka, A.; Whitcomb, D.C.; Yadav, D. Risk of and factors associated with readmission after a sentinel attack of acute pancreatitis. Clin. Gastroenterol. Hepatol. 2014, 12, 1911–1919.
  13. Hollemans, R.A.; Hallensleben, N.D.L.; Mager, D.J.; Kelder, J.C.; Besselink, M.G.; Bruno, M.J.; Verdonk, R.C.; van Santvoort, H.C. Pancreatic exocrine insufficiency following acute pancreatitis: Systematic review and study level meta-analysis. Pancreatology 2018, 18, 253–262.
  14. Huang, W.; de la Iglesia-García, D.; Baston-Rey, I.; Calviño-Suarez, C.; Lariño-Noia, J.; Iglesias-Garcia, J.; Shi, N.; Zhang, X.; Cai, W.; Deng, L.; et al. Exocrine Pancreatic Insufficiency Following Acute Pancreatitis: Systematic Review and Meta-Analysis. Dig. Dis. Sci. 2019, 64, 1985–2005.
  15. Das, S.L.; Singh, P.P.; Phillips, A.R.; Murphy, R.; Windsor, J.A.; Petrov, M.S. Newly diagnosed diabetes mellitus after acute pancreatitis: A systematic review and meta-analysis. Gut 2014, 63, 818–831.
  16. Shen, H.N.; Yang, C.C.; Chang, Y.H.; Lu, C.L.; Li, C.Y. Risk of Diabetes Mellitus after First-Attack Acute Pancreatitis: A National Population-Based Study. Am. J. Gastroenterol. 2015, 110, 1698–1706.
  17. Sadr-Azodi, O.; Oskarsson, V.; Discacciati, A.; Videhult, P.; Askling, J.; Ekbom, A. Pancreatic Cancer Following Acute Pancreatitis: A Population-based Matched Cohort Study. Am. J. Gastroenterol. 2018, 113, 1711–1719.
  18. Kirkegård, J.; Cronin-Fenton, D.; Heide-Jørgensen, U.; Mortensen, F.V. Acute Pancreatitis and Pancreatic Cancer Risk: A Nationwide Matched-Cohort Study in Denmark. Gastroenterology 2018, 154, 1729–1736.
  19. Singh, V.K.; Yadav, D.; Garg, P.K. Diagnosis and Management of Chronic Pancreatitis: A Review. JAMA 2019, 322, 2422–2434.
  20. Majumder, S.; Chari, S.T. Chronic pancreatitis. Lancet 2016, 387, 1957–1966.
  21. Lindkvist, B.; Domínguez-Muñoz, J.E.; Luaces-Regueira, M.; Castiñeiras-Alvariño, M.; Nieto-Garcia, L.; Iglesias-Garcia, J. Serum nutritional markers for prediction of pancreatic exocrine insufficiency in chronic pancreatitis. Pancreatology 2012, 12, 305–310.
  22. Layer, P.; Yamamoto, H.; Kalthoff, L.; Clain, J.E.; Bakken, L.J.; DiMagno, E.P. The different courses of early- and late-onset idiopathic and alcoholic chronic pancreatitis. Gastroenterology 1994, 107, 1481–1487.
  23. Kirkegård, J.; Mortensen, F.V.; Cronin-Fenton, D. Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis. Am. J. Gastroenterol. 2017, 112, 1366–1372.
  24. Brodovicz, K.G.; Kou, T.D.; Alexander, C.M.; O’Neill, E.A.; Engel, S.S.; Girman, C.J.; Goldstein, B.J. Impact of diabetes duration and chronic pancreatitis on the association between type 2 diabetes and pancreatic cancer risk. Diabetes Obes. Metab. 2012, 14, 1123–1128.
  25. Malka, D.; Hammel, P.; Sauvanet, A.; Rufat, P.; O’Toole, D.; Bardet, P.; Belghiti, J.; Bernades, P.; Ruszniewski, P.; Lévy, P. Risk factors for diabetes mellitus in chronic pancreatitis. Gastroenterology 2000, 119, 1324–1332.
  26. Hardt, P.D.; Killinger, A.; Nalop, J.; Schnell-Kretschmer, H.; Zekorn, T.; Klör, H.U. Chronic pancreatitis and diabetes mellitus. A retrospective analysis of 156 ERCP investigations in patients with insulin-dependent and non-insulin-dependent diabetes mellitus. Pancreatology 2002, 2, 30–33.
  27. Forsmark, C.E.; Vege, S.S.; Wilcox, C.M. Acute Pancreatitis. N. Engl. J. Med. 2016, 375, 1972–1981.
  28. Kleeff, J.; Whitcomb, D.C.; Shimosegawa, T.; Esposito, I.; Lerch, M.M.; Gress, T.; Mayerle, J.; Drewes, A.M.; Rebours, V.; Akisik, F.; et al. Chronic pancreatitis. Nat. Reviews. Dis. Primers 2017, 3, 17060.
  29. Bertilsson, S.; Swärd, P.; Kalaitzakis, E. Factors That Affect Disease Progression After First Attack of Acute Pancreatitis. Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc. 2015, 13, 1662–1669.e1663.
  30. Dreiling, D.A.; Koller, M. The natural history of alcoholic pancreatitis: Update 1985. Mt. Sinai J. Med. N. Y. 1985, 52, 340–342.
  31. Kristiansen, L.; Grønbaek, M.; Becker, U.; Tolstrup, J.S. Risk of pancreatitis according to alcohol drinking habits: A population-based cohort study. Am. J. Epidemiol. 2008, 168, 932–937.
  32. Yadav, D. Recent advances in the epidemiology of alcoholic pancreatitis. Curr. Gastroenterol. Rep. 2011, 13, 157–165.
  33. Corrao, G.; Bagnardi, V.; Zambon, A.; La Vecchia, C. A meta-analysis of alcohol consumption and the risk of 15 diseases. Prev. Med. 2004, 38, 613–619.
  34. Irving, H.M.; Samokhvalov, A.V.; Rehm, J. Alcohol as a risk factor for pancreatitis. A systematic review and meta-analysis. JOP J. Pancreas 2009, 10, 387–392.
  35. Yadav, D.; Whitcomb, D.C. The role of alcohol and smoking in pancreatitis. Nat. Rev. Gastroenterol. Hepatol. 2010, 7, 131–145.
  36. Yadav, D.; Hawes, R.H.; Brand, R.E.; Anderson, M.A.; Money, M.E.; Banks, P.A.; Bishop, M.D.; Baillie, J.; Sherman, S.; DiSario, J.; et al. Alcohol consumption, cigarette smoking, and the risk of recurrent acute and chronic pancreatitis. Arch. Intern. Med. 2009, 169, 1035–1045.
  37. Jaakkola, M.; Sillanaukee, P.; Löf, K.; Koivula, T.; Nordback, I. Amount of alcohol is an important determinant of the severity of acute alcoholic pancreatitis. Surgery 1994, 115, 31–38.
  38. Phillip, V.; Huber, W.; Hagemes, F.; Lorenz, S.; Matheis, U.; Preinfalk, S.; Schuster, T.; Lippl, F.; Saugel, B.; Schmid, R.M. Incidence of acute pancreatitis does not increase during Oktoberfest, but is higher than previously described in Germany. Clin. Gastroenterol. Hepatol. 2011, 9, 995–1000.e1003.
  39. Takeyama, Y. Long-term prognosis of acute pancreatitis in Japan. Clin. Gastroenterol. Hepatol. 2009, 7, S15–S17.
  40. Lankisch, M.R.; Imoto, M.; Layer, P.; DiMagno, E.P. The effect of small amounts of alcohol on the clinical course of chronic pancreatitis. Mayo Clin. Proc. 2001, 76, 242–251.
  41. Setiawan, V.W.; Pandol, S.J.; Porcel, J.; Wilkens, L.R.; Le Marchand, L.; Pike, M.C.; Monroe, K.R. Prospective Study of Alcohol Drinking, Smoking, and Pancreatitis: The Multiethnic Cohort. Pancreas 2016, 45, 819–825.
  42. Strum, W.B. Abstinence in alcoholic chronic pancreatitis. Effect on pain and outcome. J. Clin. Gastroenterol. 1995, 20, 37–41.
  43. Nikkola, J.; Räty, S.; Laukkarinen, J.; Seppänen, H.; Lappalainen-Lehto, R.; Järvinen, S.; Nordback, I.; Sand, J. Abstinence after first acute alcohol-associated pancreatitis protects against recurrent pancreatitis and minimizes the risk of pancreatic dysfunction. Alcohol Alcohol. 2013, 48, 483–486.
  44. Pelli, H.; Lappalainen-Lehto, R.; Piironen, A.; Sand, J.; Nordback, I. Risk factors for recurrent acute alcohol-associated pancreatitis: A prospective analysis. Scand. J. Gastroenterol. 2008, 43, 614–621.
  45. Pandol, S.J.; Lugea, A.; Mareninova, O.A.; Smoot, D.; Gorelick, F.S.; Gukovskaya, A.S.; Gukovsky, I. Investigating the pathobiology of alcoholic pancreatitis. Alcohol. Clin. Exp. Res. 2011, 35, 830–837.
  46. Sadr-Azodi, O.; Andrén-Sandberg, Å.; Orsini, N.; Wolk, A. Cigarette smoking, smoking cessation and acute pancreatitis: A prospective population-based study. Gut 2012, 61, 262–267.
  47. Lin, Y.; Tamakoshi, A.; Hayakawa, T.; Ogawa, M.; Ohno, Y. Cigarette smoking as a risk factor for chronic pancreatitis: A case-control study in Japan. Research Committee on Intractable Pancreatic Diseases. Pancreas 2000, 21, 109–114.
  48. Lowenfels, A.B.; Maisonneuve, P.; Whitcomb, D.C.; Lerch, M.M.; DiMagno, E.P. Cigarette smoking as a risk factor for pancreatic cancer in patients with hereditary pancreatitis. JAMA 2001, 286, 169–170.
  49. Fuchs, C.S.; Colditz, G.A.; Stampfer, M.J.; Giovannucci, E.L.; Hunter, D.J.; Rimm, E.B.; Willett, W.C.; Speizer, F.E. A prospective study of cigarette smoking and the risk of pancreatic cancer. Arch. Intern. Med. 1996, 156, 2255–2260.
  50. Greer, J.B.; Thrower, E.; Yadav, D. Epidemiologic and Mechanistic Associations Between Smoking and Pancreatitis. Curr. Treat. Options Gastroenterol. 2015, 13, 332–346.
  51. Talamini, G.; Bassi, C.; Falconi, M.; Frulloni, L.; Di Francesco, V.; Vaona, B.; Bovo, P.; Rigo, L.; Castagnini, A.; Angelini, G.; et al. Cigarette smoking: An independent risk factor in alcoholic pancreatitis. Pancreas 1996, 12, 131–137.
  52. Maisonneuve, P.; Lowenfels, A.B.; Müllhaupt, B.; Cavallini, G.; Lankisch, P.G.; Andersen, J.R.; Dimagno, E.P.; Andrén-Sandberg, A.; Domellöf, L.; Frulloni, L.; et al. Cigarette smoking accelerates progression of alcoholic chronic pancreatitis. Gut 2005, 54, 510–514.
  53. Zhu, Y.; Pan, X.; Zeng, H.; He, W.; Xia, L.; Liu, P.; Zhu, Y.; Chen, Y.; Lv, N. A Study on the Etiology, Severity, and Mortality of 3260 Patients With Acute Pancreatitis According to the Revised Atlanta Classification in Jiangxi, China Over an 8-Year Period. Pancreas 2017, 46, 504–509.
  54. Toskes, P.P. Hyperlipidemic pancreatitis. Gastroenterol. Clin. N. Am. 1990, 19, 783–791.
  55. Vipperla, K.; Somerville, C.; Furlan, A.; Koutroumpakis, E.; Saul, M.; Chennat, J.; Rabinovitz, M.; Whitcomb, D.C.; Slivka, A.; Papachristou, G.I.; et al. Clinical Profile and Natural Course in a Large Cohort of Patients With Hypertriglyceridemia and Pancreatitis. J. Clin. Gastroenterol. 2017, 51, 77–85.
  56. Klop, B.; do Rego, A.T.; Cabezas, M.C. Alcohol and plasma triglycerides. Curr. Opin. Lipidol. 2013, 24, 321–326.
  57. Bessembinders, K.; Wielders, J.; van de Wiel, A. Severe hypertriglyceridemia influenced by alcohol (SHIBA). Alcohol Alcohol. 2011, 46, 113–116.
  58. Garg, R.; Rustagi, T. Management of Hypertriglyceridemia Induced Acute Pancreatitis. BioMed Res. Int. 2018, 2018, 4721357.
  59. Fortson, M.R.; Freedman, S.N.; Webster, P.D., 3rd. Clinical assessment of hyperlipidemic pancreatitis. Am. J. Gastroenterol. 1995, 90, 2134–2139.
  60. Rosenthal, R.; Günzel, D.; Krug, S.M.; Schulzke, J.D.; Fromm, M.; Yu, A.S. Claudin-2-mediated cation and water transport share a common pore. Acta Physiol. 2017, 219, 521–536.
  61. Aung, P.P.; Mitani, Y.; Sanada, Y.; Nakayama, H.; Matsusaki, K.; Yasui, W. Differential expression of claudin-2 in normal human tissues and gastrointestinal carcinomas. Virchows Arch. 2006, 448, 428–434.
  62. Whitcomb, D.C.; LaRusch, J.; Krasinskas, A.M.; Klei, L.; Smith, J.P.; Brand, R.E.; Neoptolemos, J.P.; Lerch, M.M.; Tector, M.; Sandhu, B.S.; et al. Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis. Nat. Genet. 2012, 44, 1349–1354.
  63. Rosendahl, J.; Kirsten, H.; Hegyi, E.; Kovacs, P.; Weiss, F.U.; Laumen, H.; Lichtner, P.; Ruffert, C.; Chen, J.M.; Masson, E.; et al. Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis. Gut 2018, 67, 1855–1863.
  64. Yang, A.L.; Vadhavkar, S.; Singh, G.; Omary, M.B. Epidemiology of alcohol-related liver and pancreatic disease in the United States. Arch. Intern. Med. 2008, 168, 649–656.
  65. Wilcox, C.M.; Sandhu, B.S.; Singh, V.; Gelrud, A.; Abberbock, J.N.; Sherman, S.; Cote, G.A.; Al-Kaade, S.; Anderson, M.A.; Gardner, T.B.; et al. Racial Differences in the Clinical Profile, Causes, and Outcome of Chronic Pancreatitis. Am. J. Gastroenterol. 2016, 111, 1488–1496.
  66. Lin, H.H.; Chang, H.Y.; Chiang, Y.T.; Wu, M.S.; Lin, J.T.; Liao, W.C. Smoking, drinking, and pancreatitis: A population-based cohort study in Taiwan. Pancreas 2014, 43, 1117–1122.
  67. Samokhvalov, A.V.; Rehm, J.; Roerecke, M. Alcohol Consumption as a Risk Factor for Acute and Chronic Pancreatitis: A Systematic Review and a Series of Meta-analyses. EBioMedicine 2015, 2, 1996–2002.
  68. Kume, K.; Masamune, A.; Ariga, H.; Shimosegawa, T. Alcohol Consumption and the Risk for Developing Pancreatitis: A Case-Control Study in Japan. Pancreas 2015, 44, 53–58.
  69. Chen, Y.J.; Chen, C.; Wu, D.C.; Lee, C.H.; Wu, C.I.; Lee, J.M.; Goan, Y.G.; Huang, S.P.; Lin, C.C.; Li, T.C.; et al. Interactive effects of lifetime alcohol consumption and alcohol and aldehyde dehydrogenase polymorphisms on esophageal cancer risks. Int. J. Cancer 2006, 119, 2827–2831.
  70. Lee, C.H.; Lee, J.M.; Wu, D.C.; Goan, Y.G.; Chou, S.H.; Wu, I.C.; Kao, E.L.; Chan, T.F.; Huang, M.C.; Chen, P.S.; et al. Carcinogenetic impact of ADH1B and ALDH2 genes on squamous cell carcinoma risk of the esophagus with regard to the consumption of alcohol, tobacco and betel quid. Int. J. Cancer 2008, 122, 1347–1356.
  71. Yokoyama, A.; Mizukami, T.; Matsui, T.; Yokoyama, T.; Kimura, M.; Matsushita, S.; Higuchi, S.; Maruyama, K. Genetic polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 and liver cirrhosis, chronic calcific pancreatitis, diabetes mellitus, and hypertension among Japanese alcoholic men. Alcohol. Clin. Exp. Res. 2013, 37, 1391–1401.
  72. Gukovsky, I.; Lugea, A.; Shahsahebi, M.; Cheng, J.H.; Hong, P.P.; Jung, Y.J.; Deng, Q.G.; French, B.A.; Lungo, W.; French, S.W.; et al. A rat model reproducing key pathological responses of alcoholic chronic pancreatitis. Am. J. Physiol. Gastrointest. Liver Physiol. 2008, 294, G68–G79.
  73. Schneider, L.; Pietschmann, M.; Hartwig, W.; Hackert, T.; Marcos, S.S.; Longerich, T.; Gebhard, M.M.; Büchler, M.W.; Werner, J. Alcohol pretreatment increases hepatic and pulmonary injury in experimental pancreatitis. Pancreatology 2009, 9, 258–266.
  74. Lugea, A.; Tischler, D.; Nguyen, J.; Gong, J.; Gukovsky, I.; French, S.W.; Gorelick, F.S.; Pandol, S.J. Adaptive unfolded protein response attenuates alcohol-induced pancreatic damage. Gastroenterology 2011, 140, 987–997.
  75. Ren, Z.; Wang, X.; Xu, M.; Yang, F.; Frank, J.A.; Ke, Z.J.; Luo, J. Binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas. Oncotarget 2016, 7, 54303–54316.
  76. Ren, Z.; Yang, F.; Wang, X.; Wang, Y.; Xu, M.; Frank, J.A.; Ke, Z.J.; Zhang, Z.; Shi, X.; Luo, J. Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation. Toxicol. Appl. Pharmacol. 2016, 308, 11–19.
  77. Bertola, A.; Mathews, S.; Ki, S.H.; Wang, H.; Gao, B. Mouse model of chronic and binge ethanol feeding (the NIAAA model). Nat. Protoc. 2013, 8, 627–637.
  78. Wang, S.; Ni, H.M.; Chao, X.; Ma, X.; Kolodecik, T.; De Lisle, R.; Ballabio, A.; Pacher, P.; Ding, W.X. Critical Role of TFEB-Mediated Lysosomal Biogenesis in Alcohol-Induced Pancreatitis in Mice and Humans. Cell. Mol. Gastroenterol. Hepatol. 2020, 10, 59–81.
  79. Sloan, F.; Grossman, D.; Platt, A. Heavy episodic drinking in early adulthood and outcomes in midlife. J. Stud. Alcohol Drugs 2011, 72, 459–470.
  80. Choi, G.; Runyon, B.A. Alcoholic hepatitis: A clinician’s guide. Clin. Liver Dis. 2012, 16, 371–385.
  81. Mathurin, P.; Lucey, M.R. Management of alcoholic hepatitis. J. Hepatol. 2012, 56 (Suppl. 1), S39–S45.
  82. Ki, S.H.; Park, O.; Zheng, M.; Morales-Ibanez, O.; Kolls, J.K.; Bataller, R.; Gao, B. Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: Role of signal transducer and activator of transcription 3. Hepatology 2010, 52, 1291–1300.
  83. Gao, B.; Xu, M.J.; Bertola, A.; Wang, H.; Zhou, Z.; Liangpunsakul, S. Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance. Gene Expr. 2017, 17, 173–186.
  84. Lieber, C.S.; DeCarli, L.M. Ethanol oxidation by hepatic microsomes: Adaptive increase after ethanol feeding. Science 1968, 162, 917–918.
  85. Mello, T.; Ceni, E.; Surrenti, C.; Galli, A. Alcohol induced hepatic fibrosis: Role of acetaldehyde. Mol. Asp. Med. 2008, 29, 17–21.
  86. Zakhari, S. Overview: How is alcohol metabolized by the body? Alcohol research & health: The journal of the National Institute on Alcohol Abuse and Alcoholism 2006, 29, 245–254.
  87. Guerri, C.; Sanchis, R. Acetaldehyde and alcohol levels in pregnant rats and their fetuses. Alcohol 1985, 2, 267–270.
  88. Eriksson, C.J.; Sippel, H.W. The distribution and metabolism of acetaldehyde in rats during ethanol oxidation-I. The distribution of acetaldehyde in liver, brain, blood and breath. Biochem. Pharmacol. 1977, 26, 241–247.
  89. Laposata, E.A.; Lange, L.G. Presence of nonoxidative ethanol metabolism in human organs commonly damaged by ethanol abuse. Science 1986, 231, 497–499.
  90. Werner, J.; Laposata, M.; Fernández-del Castillo, C.; Saghir, M.; Iozzo, R.V.; Lewandrowski, K.B.; Warshaw, A.L. Pancreatic injury in rats induced by fatty acid ethyl ester, a nonoxidative metabolite of alcohol. Gastroenterology 1997, 113, 286–294.
  91. Werner, J.; Saghir, M.; Warshaw, A.L.; Lewandrowski, K.B.; Laposata, M.; Iozzo, R.V.; Carter, E.A.; Schatz, R.J.; Fernández-Del Castillo, C. Alcoholic pancreatitis in rats: Injury from nonoxidative metabolites of ethanol. Am. J. Physiol. Gastrointest. Liver Physiol. 2002, 283, G65–G73.
  92. Huang, W.; Booth, D.M.; Cane, M.C.; Chvanov, M.; Javed, M.A.; Elliott, V.L.; Armstrong, J.A.; Dingsdale, H.; Cash, N.; Li, Y.; et al. Fatty acid ethyl ester synthase inhibition ameliorates ethanol-induced Ca2+-dependent mitochondrial dysfunction and acute pancreatitis. Gut 2014, 63, 1313–1324.
  93. Lampel, M.; Kern, H.F. Acute interstitial pancreatitis in the rat induced by excessive doses of a pancreatic secretagogue. Virchows Archiv. A Pathol. Anat. Histol. 1977, 373, 97–117.
  94. Wisner, J.; Green, D.; Ferrell, L.; Renner, I. Evidence for a role of oxygen derived free radicals in the pathogenesis of caerulein induced acute pancreatitis in rats. Gut 1988, 29, 1516–1523.
  95. Pandol, S.J.; Periskic, S.; Gukovsky, I.; Zaninovic, V.; Jung, Y.; Zong, Y.; Solomon, T.E.; Gukovskaya, A.S.; Tsukamoto, H. Ethanol diet increases the sensitivity of rats to pancreatitis induced by cholecystokinin octapeptide. Gastroenterology 1999, 117, 706–716.
  96. Rongione, A.J.; Kusske, A.M.; Kwan, K.; Ashley, S.W.; Reber, H.A.; McFadden, D.W. Interleukin 10 reduces the severity of acute pancreatitis in rats. Gastroenterology 1997, 112, 960–967.
  97. Virlos, I.; Mazzon, E.; Serraino, I.; Di Paola, R.; Genovese, T.; Britti, D.; Thiemerman, C.; Siriwardena, A.; Cuzzocrea, S. Pyrrolidine dithiocarbamate reduces the severity of cerulein-induced murine acute pancreatitis. Shock 2003, 20, 544–550.
  98. Niederau, C.; Ferrell, L.D.; Grendell, J.H. Caerulein-induced acute necrotizing pancreatitis in mice: Protective effects of proglumide, benzotript, and secretin. Gastroenterology 1985, 88, 1192–1204.
  99. Demols, A.; Van Laethem, J.L.; Quertinmont, E.; Legros, F.; Louis, H.; Le Moine, O.; Devière, J. N-acetylcysteine decreases severity of acute pancreatitis in mice. Pancreas 2000, 20, 161–169.
  100. Genovese, T.; Mazzon, E.; Di Paola, R.; Muià, C.; Crisafulli, C.; Menegazzi, M.; Malleo, G.; Suzuki, H.; Cuzzocrea, S. Hypericum perforatum attenuates the development of cerulein-induced acute pancreatitis in mice. Shock 2006, 25, 161–167.
  101. Bartholomew, C. Acute scorpion pancreatitis in Trinidad. Br. Med. J. 1970, 1, 666–668.
  102. Singh, S.; Bhardwaj, U.; Verma, S.K.; Bhalla, A.; Gill, K. Hyperamylasemia and acute pancreatitis following anticholinesterase poisoning. Hum. Exp. Toxicol. 2007, 26, 467–471.
  103. Becerril, B.; Marangoni, S.; Possani, L.D. Toxins and genes isolated from scorpions of the genus Tityus. Toxicon 1997, 35, 821–835.
  104. Fletcher, P.L., Jr.; Fletcher, M.D.; Possani, L.D. Characteristics of pancreatic exocrine secretion produced by venom from the Brazilian scorpion, Tityus serrulatus. Eur. J. Cell Biol. 1992, 58, 259–270.
  105. Quon, M.G.; Kugelmas, M.; Wisner, J.R., Jr.; Chandrasoma, P.; Valenzuela, J.E. Chronic alcohol consumption intensifies caerulein-induced acute pancreatitis in the rat. Int. J. Pancreatol. 1992, 12, 31–39.
  106. Neuschwander-Tetri, B.A.; Burton, F.R.; Presti, M.E.; Britton, R.S.; Janney, C.G.; Garvin, P.R.; Brunt, E.M.; Galvin, N.J.; Poulos, J.E. Repetitive self-limited acute pancreatitis induces pancreatic fibrogenesis in the mouse. Dig. Dis. Sci. 2000, 45, 665–674.
  107. Ulmasov, B.; Oshima, K.; Rodriguez, M.G.; Cox, R.D.; Neuschwander-Tetri, B.A. Differences in the degree of cerulein-induced chronic pancreatitis in C57BL/6 mouse substrains lead to new insights in identification of potential risk factors in the development of chronic pancreatitis. Am. J. Pathol. 2013, 183, 692–708.
  108. Deng, X.; Wang, L.; Elm, M.S.; Gabazadeh, D.; Diorio, G.J.; Eagon, P.K.; Whitcomb, D.C. Chronic alcohol consumption accelerates fibrosis in response to cerulein-induced pancreatitis in rats. Am. J. Pathol. 2005, 166, 93–106.
  109. Perides, G.; Tao, X.; West, N.; Sharma, A.; Steer, M.L. A mouse model of ethanol dependent pancreatic fibrosis. Gut 2005, 54, 1461–1467.
  110. Vonlaufen, A.; Xu, Z.; Daniel, B.; Kumar, R.K.; Pirola, R.; Wilson, J.; Apte, M.V. Bacterial endotoxin: A trigger factor for alcoholic pancreatitis? Evidence from a novel, physiologically relevant animal model. Gastroenterology 2007, 133, 1293–1303.
  111. Farhana, A.; Khan, Y.S. Biochemistry, Lipopolysaccharide. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2021.
  112. Bode, C.; Kugler, V.; Bode, J.C. Endotoxemia in patients with alcoholic and non-alcoholic cirrhosis and in subjects with no evidence of chronic liver disease following acute alcohol excess. J. Hepatol. 1987, 4, 8–14.
  113. Fukui, H.; Brauner, B.; Bode, J.C.; Bode, C. Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: Reevaluation with an improved chromogenic assay. J. Hepatol. 1991, 12, 162–169.
  114. Ammori, B.J.; Leeder, P.C.; King, R.F.; Barclay, G.R.; Martin, I.G.; Larvin, M.; McMahon, M.J. Early increase in intestinal permeability in patients with severe acute pancreatitis: Correlation with endotoxemia, organ failure, and mortality. J. Gastrointest. Surg. 1999, 3, 252–262.
  115. Fortunato, F.; Deng, X.; Gates, L.K.; McClain, C.J.; Bimmler, D.; Graf, R.; Whitcomb, D.C. Pancreatic response to endotoxin after chronic alcohol exposure: Switch from apoptosis to necrosis? Am. J. Physiol. Gastrointest. Liver Physiol. 2006, 290, G232–G241.
  116. Vonlaufen, A.; Phillips, P.A.; Xu, Z.; Zhang, X.; Yang, L.; Pirola, R.C.; Wilson, J.S.; Apte, M.V. Withdrawal of alcohol promotes regression while continued alcohol intake promotes persistence of LPS-induced pancreatic injury in alcohol-fed rats. Gut 2011, 60, 238–246.
  117. Gu, H.; Werner, J.; Bergmann, F.; Whitcomb, D.C.; Büchler, M.W.; Fortunato, F. Necro-inflammatory response of pancreatic acinar cells in the pathogenesis of acute alcoholic pancreatitis. Cell Death Dis. 2013, 4, e816.
  118. Grauvogel, J.; Daemmrich, T.D.; Ryschich, E.; Gebhard, M.M.; Werner, J. Chronic alcohol intake increases the severity of pancreatitis induced by acute alcohol administration, hyperlipidemia and pancreatic duct obstruction in rats. Pancreatology 2010, 10, 603–612.
  119. Tanaka, T.; Miura, Y.; Matsugu, Y.; Ichiba, Y.; Ito, H.; Dohi, K. Pancreatic duct obstruction is an aggravating factor in the canine model of chronic alcoholic pancreatitis. Gastroenterology 1998, 115, 1248–1253.
  120. Orekhova, A.; Geisz, A.; Sahin-Tóth, M. Ethanol feeding accelerates pancreatitis progression in CPA1 N256K mutant mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2020, 318, G694–G704.
  121. Sun, J.; Fu, J.; Zhong, Y.; Li, L.; Chen, C.; Wang, X.; Wang, L.; Hou, Y.; Wang, H.; Zhao, R.; et al. NRF2 mitigates acute alcohol-induced hepatic and pancreatic injury in mice. Food Chem. Toxicol. 2018, 121, 495–503.
  122. Amsterdam, A.; Jamieson, J.D. Structural and functional characterization of isolated pancreatic exocrine cells. Proc. Natl. Acad. Sci. USA 1972, 69, 3028–3032.
  123. Saluja, A.; Dudeja, V.; Dawra, R.; Sah, R.P. Early Intra-Acinar Events in Pathogenesis of Pancreatitis. Gastroenterology 2019, 156, 1979–1993.
  124. Steer, M.L. Early events in acute pancreatitis. Best Pract. Res.. Clin. Gastroenterol. 1999, 13, 213–225.
  125. Gorelick, F.S.; Thrower, E. The acinar cell and early pancreatitis responses. Clin. Gastroenterol. Hepatol 2009, 7, S10–S14.
  126. Subramanya, S.B.; Subramanian, V.S.; Sekar, V.T.; Said, H.M. Thiamin uptake by pancreatic acinar cells: Effect of chronic alcohol feeding/exposure. Am. J. Physiol. Gastrointest. Liver Physiol. 2011, 301, G896–G904.
  127. Srinivasan, P.; Nabokina, S.; Said, H.M. Chronic alcohol exposure affects pancreatic acinar mitochondrial thiamin pyrophosphate uptake: Studies with mouse 266-6 cell line and primary cells. Am. J. Physiol. Gastrointest. Liver Physiol. 2015, 309, G750–G758.
  128. Singh, M. Effect of thiamin deficiency on pancreatic acinar cell function. Am. J. Clin. Nutr. 1982, 36, 500–504.
  129. Rathanaswami, P.; Pourany, A.; Sundaresan, R. Effects of thiamine deficiency on the secretion of insulin and the metabolism of glucose in isolated rat pancreatic islets. Biochem. Int. 1991, 25, 577–583.
  130. Rathanaswami, P.; Sundaresan, R. Effects of thiamine deficiency on the biosynthesis of insulin in rats. Biochem. Int. 1991, 24, 1057–1062.
  131. Wu, H.; Bhopale, K.K.; Ansari, G.A.; Kaphalia, B.S. Ethanol-induced cytotoxicity in rat pancreatic acinar AR42J cells: Role of fatty acid ethyl esters. Alcohol Alcohol. 2008, 43, 1–8.
  132. Lugea, A.; Gerloff, A.; Su, H.Y.; Xu, Z.; Go, A.; Hu, C.; French, S.W.; Wilson, J.S.; Apte, M.V.; Waldron, R.T.; et al. The Combination of Alcohol and Cigarette Smoke Induces Endoplasmic Reticulum Stress and Cell Death in Pancreatic Acinar Cells. Gastroenterology 2017, 153, 1674–1686.
  133. González, A.; Pariente, J.A.; Salido, G.M. Ethanol impairs calcium homeostasis following CCK-8 stimulation in mouse pancreatic acinar cells. Alcohol 2008, 42, 565–573.
  134. Fernández-Sánchez, M.; del Castillo-Vaquero, A.; Salido, G.M.; González, A. Ethanol exerts dual effects on calcium homeostasis in CCK-8-stimulated mouse pancreatic acinar cells. BMC Cell Biol. 2009, 10, 77.
  135. González, A.; Núñez, A.M.; Granados, M.P.; Pariente, J.A.; Salido, G.M. Ethanol impairs CCK-8-evoked amylase secretion through Ca2+-mediated ROS generation in mouse pancreatic acinar cells. Alcohol 2006, 38, 51–57.
  136. Orabi, A.I.; Shah, A.U.; Muili, K.; Luo, Y.; Mahmood, S.M.; Ahmad, A.; Reed, A.; Husain, S.Z. Ethanol enhances carbachol-induced protease activation and accelerates Ca2+ waves in isolated rat pancreatic acini. J. Biol. Chem. 2011, 286, 14090–14097.
  137. Hegyi, P.; Pandol, S.; Venglovecz, V.; Rakonczay, Z., Jr. The acinar-ductal tango in the pathogenesis of acute pancreatitis. Gut 2011, 60, 544–552.
  138. Wilschanski, M.; Novak, I. The cystic fibrosis of exocrine pancreas. Cold Spring Harb. Perspect. Med. 2013, 3, a009746.
  139. Larusch, J.; Whitcomb, D.C. Genetics of pancreatitis with a focus on the pancreatic ducts. Minerva Gastroenterol. E Dietol. 2012, 58, 299–308.
  140. Sarles, H.; Sarles, J.C.; Camatte, R.; Muratore, R.; Gaini, M.; Guien, C.; Pastor, J.; Le Roy, F. Observations on 205 confirmed cases of acute pancreatitis, recurring pancreatitis, and chronic pancreatitis. Gut 1965, 6, 545–559.
  141. Sharer, N.; Schwarz, M.; Malone, G.; Howarth, A.; Painter, J.; Super, M.; Braganza, J. Mutations of the cystic fibrosis gene in patients with chronic pancreatitis. N. Engl. J. Med. 1998, 339, 645–652.
  142. Maléth, J.; Balázs, A.; Pallagi, P.; Balla, Z.; Kui, B.; Katona, M.; Judák, L.; Németh, I.; Kemény, L.V.; Rakonczay, Z., Jr.; et al. Alcohol disrupts levels and function of the cystic fibrosis transmembrane conductance regulator to promote development of pancreatitis. Gastroenterology 2015, 148, 427–439.e416.
More
Information
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
View Times: 793
Revisions: 2 times (View History)
Update Date: 19 Apr 2022
1000/1000
Video Production Service