Melatonin, a derivative of the amino acid tryptophan, was initially thought to be mainly produced and secreted by the pineal gland; with time, it was also found in other tissues and organs, and even in plants. Since its discovery, the study of the role of the indole in cellular homeostasis has generated impressive data, which have led researchers to a common idea regarding the positive actions of melatonin in health. The uncontrolled production of free radicals in cellular systems leads to the situation termed oxidative stress, which has been signaled as the basis of disease and aging. In the exocrine pancreas, as in other parts of the body, a daily confrontation takes place against oxidative stress. The major signaling mechanisms controlling the physiology of the gland are affected under this situation. Because a love-hate relationship involving mitochondria and oxidative stress has been considered the basis of disease, any physiological regulator that sets hands on the system as a pacemaker will be determinant for the health's fate. Here we present an overview of the recent findings regarding the protective role of melatonin on the function of the exocrine pancreas, paying attention to the role of Ca2+ signaling and the involvement of mitochondria.
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