BACKGROUND: Chronic alcohol consumption increases the risk of pancreatitis in humans. Functional hyperstimulation/hypersecretion of the pancreas during chronic alcohol consumption appears to precede the onset of pancreatitis, and may contribute to the increased susceptibility to pancreatitis in alcoholics. However, the origin, nature and timing of hyperstimulation/hypersecretion are unknown. METHODS: Male Wistar rats were pair-fed ethanol liquid diet for 15-18 days (including one 9-day dose ramp-up phase) or regular liquid diets before placement of pancreatic, biliary, duodenal and venous catheters. Basal and stimulated pancreatic secretions were measured with or without acute alcohol infusion. Pancreatic secretion was stimulated with intravenous bethanechol, 2-deoxy-D-glucose (2-DG), cholecystokinin (CCK), octapeptide (CCK-8), intraduodenal meal, or vehicle. RESULTS: Acute alcohol potentiated 2-DG stimulated pancreatic secretion (184%, p < 0.05), whereas the response to CCK was unchanged, and the response to bethanechol was decreased (78%, p < 0.05). Short-term alcohol exposure lessened the exaggerated protein secretory response to 2-DG seen in acute alcohol exposure rats and increased the protein response to bethanechol (141%, p < 0.05), CCK (187%, p < 0.05) and meal (217%, p < 0.05). CONCLUSION: The pancreas is sensitive to acute alcohol ingestion with inhibition of acinar cell function. Rapid adaptation occurs with short-term alcohol feeding, resulting in an exaggerated response to cholinergic input at the acinar cells, plus disinhibition of CCK and meal-stimulated pancreatic secretion. The central response to 2-DG and CCK are similar to area postrema lesions. Adaptation appears to be in response to alcohol-associated inhibition of the neurohormonal stimulatory pathway and compensatory upregulation at the acinar cell level.
BACKGROUND: Chronic alcohol consumption increases the risk of pancreatitis in humans. Functional hyperstimulation/hypersecretion of the pancreas during chronic alcohol consumption appears to precede the onset of pancreatitis, and may contribute to the increased susceptibility to pancreatitis in alcoholics. However, the origin, nature and timing of hyperstimulation/hypersecretion are unknown. METHODS: Male Wistar rats were pair-fed ethanol liquid diet for 15-18 days (including one 9-day dose ramp-up phase) or regular liquid diets before placement of pancreatic, biliary, duodenal and venous catheters. Basal and stimulated pancreatic secretions were measured with or without acute alcohol infusion. Pancreatic secretion was stimulated with intravenous bethanechol, 2-deoxy-D-glucose (2-DG), cholecystokinin (CCK), octapeptide (CCK-8), intraduodenal meal, or vehicle. RESULTS: Acute alcohol potentiated 2-DG stimulated pancreatic secretion (184%, p < 0.05), whereas the response to CCK was unchanged, and the response to bethanechol was decreased (78%, p < 0.05). Short-term alcohol exposure lessened the exaggerated protein secretory response to 2-DG seen in acute alcohol exposure rats and increased the protein response to bethanechol (141%, p < 0.05), CCK (187%, p < 0.05) and meal (217%, p < 0.05). CONCLUSION: The pancreas is sensitive to acute alcohol ingestion with inhibition of acinar cell function. Rapid adaptation occurs with short-term alcohol feeding, resulting in an exaggerated response to cholinergic input at the acinar cells, plus disinhibition of CCK and meal-stimulated pancreatic secretion. The central response to 2-DG and CCK are similar to area postrema lesions. Adaptation appears to be in response to alcohol-associated inhibition of the neurohormonal stimulatory pathway and compensatory upregulation at the acinar cell level.
Authors: Aurelia Lugea; Jun Gong; Janie Nguyen; Jose Nieto; Samuel W French; Stephen J Pandol Journal: Alcohol Clin Exp Res Date: 2010-07-09 Impact factor: 3.455
Authors: Xiaoying Deng; Lin Wang; Mary S Elm; David Gabazadeh; Greg J Diorio; Patricia K Eagon; David C Whitcomb Journal: Am J Pathol Date: 2005-01 Impact factor: 4.307