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Effects of Melatonin and Its Analogues on Pancreatic Inflammation, Enzyme Secretion, and Tumorigenesis

Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University Medical College, 31-126 Kraków, Poland
Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Kraków, Poland
Author to whom correspondence should be addressed.
Academic Editor: Russel J. Reiter
Int. J. Mol. Sci. 2017, 18(5), 1014;
Received: 30 March 2017 / Revised: 26 April 2017 / Accepted: 2 May 2017 / Published: 8 May 2017
(This article belongs to the Special Issue Melatonin and Its Analogues: Experimental and Clinical Aspects)
Melatonin is an indoleamine produced from the amino acid l-tryptophan, whereas metabolites of melatonin are known as kynuramines. One of the best-known kynuramines is N1-acetyl-N1-formyl-5-methoxykynuramine (AFMK). Melatonin has attracted scientific attention as a potent antioxidant and protector of tissue against oxidative stress. l-Tryptophan and kynuramines share common beneficial features with melatonin. Melatonin was originally discovered as a pineal product, has been detected in the gastrointestinal tract, and its receptors have been identified in the pancreas. The role of melatonin in the pancreatic gland is not explained, however several arguments support the opinion that melatonin is probably implicated in the physiology and pathophysiology of the pancreas. (1) Melatonin stimulates pancreatic enzyme secretion through the activation of entero-pancreatic reflex and cholecystokinin (CCK) release. l-Tryptophan and AFMK are less effective than melatonin in the stimulation of pancreatic exocrine function; (2) Melatonin is a successful pancreatic protector, which prevents the pancreas from developing of acute pancreatitis and reduces pancreatic damage. This effect is related to its direct and indirect antioxidant action, to the strengthening of immune defense, and to the modulation of apoptosis. Like melatonin, its precursor and AFMK are able to mimic its protective effect, and it is commonly accepted that all these substances create an antioxidant cascade to intensify the pancreatic protection and acinar cells viability; (3) In pancreatic cancer cells, melatonin and AFMK activated a signal transduction pathway for apoptosis and stimulated heat shock proteins. The role of melatonin and AFMK in pancreatic tumorigenesis remains to be elucidated. View Full-Text
Keywords: melatonin; AFMK; enzyme secretion; acute pancreatitis; pancreatic cancer melatonin; AFMK; enzyme secretion; acute pancreatitis; pancreatic cancer
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Jaworek, J.; Leja-Szpak, A.; Nawrot-Porąbka, K.; Szklarczyk, J.; Kot, M.; Pierzchalski, P.; Góralska, M.; Ceranowicz, P.; Warzecha, Z.; Dembinski, A.; Bonior, J. Effects of Melatonin and Its Analogues on Pancreatic Inflammation, Enzyme Secretion, and Tumorigenesis. Int. J. Mol. Sci. 2017, 18, 1014.

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