Pathophysiological Effects of Nicotine on the Pancreas: An Update

Abstract

Epidemiological evidence strongly suggests an association between cigarette smoking and pancreatic diseases. It is well recognized that nicotine, a major component in cigarette smoke, is an addictive agent and, therefore, reinforces smoking behavior. The current review update focuses on the genetics of nicotine dependence and its role on the development of pancreatic diseases. The role of smoking and nicotine in pancreatitis and pancreatic cancer development is also discussed. Exposure of laboratory animals to nicotine clearly supports the notion that nicotine can induce pancreatic injury. The mechanism by which nicotine induces such effects is perhaps mediated via signal transduction pathways in the pancreatic acinar cell, leading to enhanced levels of intracellular calcium release, resulting in cytotoxicity and eventual cell death. The induction of pancreatic injury by nicotine may also involve activation and expression of protooncogene, H-ras, which can increase cytosolic calcium via second messenger pathways. Development of pancreatic carcinoma in cigarette smokers as observed in human populations may be the result of activation and mutation of the H-ras gene. A possible pathogenetic mechanism of nicotine in the pancreas activating multiple signal transduction pathways is schematically summarized in Figure 1.

Potential carcinogenic effects of cigarette smoke and Swedish moist snuff on pancreas: a study using a transgenic mouse model of chronic pancreatitis

“…The proposed mechanisms underlying nicotine-induced acinar injury include intracellular calcium mobilization and activation of calmodulin-dependent protein kinases resulting in cytotoxicity and eventual cell death. 44 However, in this study, we did not observe similar morphological changes in the acinar cells of tobacco-treated WT mice. In addition to the species differences, the nicotine intake by mice in our study was found to be much lower, o0.6 mg per day of Snus-treated mice and o0.1 mg per day of TS-treated WT, compared with an estimate of 415 mg per day in Chowdhury's study.…”

Association of passive and active smoking with incident type 2 diabetes mellitus in the elderly population: the KORA S4/F4 cohort study

“…Thus, abdominal obesity, which is a strong risk factor for T2DM [37], is more prevalent in smokers. Furthermore, tobacco ingredients are likely to have toxic effects on the pancreas [38], a finding which is consistent with a higher risk of pancreatic cancer in smokers [39]. Furthermore, elevated levels of C-reactive protein [40,41] and plasma fibrinogen [30,40,41] have been found in smokers, suggesting that tobacco smoke might activate inflammation leading to T2DM.…”

Cigarette smoke-induced pancreatic damage—experimental data

“…Therefore, it is almost impossible to identify one substance responsible for one specific action because of the likely interactions of different chemicals, an uncomfortable situation for basic scientists. As a consequence, most studies either investigated the biological effect of tobacco smokederived substances with carcinogenic potential on the pancreas or investigated pancreatic alterations induced by pharmacologically active substances such as nicotine [8][9][10]. This strict separation of carcinogenic events from interference with regulatory events however, has to be undertaken with caution because recent studies indicate that carcinogenic substances as for instance 4-(methylnitrosamino)-1-(3-pyridil)-1-butanone (NNK) also exert widespread pharmacological actions [11].…”

“…In addition to these carcinogenic events, the pharmacologically active substance nicotine contained in cigarette smoke has shown to induce morphologic pancreatic alterations as well [10,16]. The mechanism by which nicotine relays its effects on the pancreatic gland is believed to be mediated by nicotinergic acetylcholine receptors, which are ubiquitously expressed and are also involved physiologically in the regulation of pancreatic enzyme secretion [17].…”