Abstract
Melatonin, N-acetyl-5-methoxytryptamine, is an indole mainly synthesized from tryptophan in the pineal gland and secreted exclusively during the night in all the animals reported to date. While the pineal gland is the major source responsible for this night rise, it is not at all the exclusive production site and many other tissues and organs produce melatonin as well. Likewise, melatonin is not restricted to vertebrates, as its presence has been reported in almost all the phyla from protozoa to mammals. Melatonin displays a large set of functions including adaptation to light: dark cycles, free radical scavenging ability, antioxidant enzyme modulation, immunomodulatory actions or differentiation–proliferation regulatory effects, among others. However, in addition to those important functions, this evolutionary ‘ancient’ molecule still hides further tools with important cellular implications. The major goal of the present review is to discuss the data and experiments that have addressed the relationship between the indole and glucose. Classically, the pineal gland and a pinealectomy were associated with glucose homeostasis even before melatonin was chemically isolated. Numerous reports have provided the molecular components underlying the regulatory actions of melatonin on insulin secretion in pancreatic beta-cells, mainly involving membrane receptors MTNR1A/B, which would be partially responsible for the circadian rhythmicity of insulin in the organism. More recently, a new line of evidence has shown that glucose transporters GLUT/SLC2A are linked to melatonin uptake and its cellular internalization. Beside its binding to membrane receptors, melatonin transportation into the cytoplasm, required for its free radical scavenging abilities, still generates a great deal of debate. Thus, GLUT transporters might constitute at least one of the keys to explain the relationship between glucose and melatonin. These and other potential mechanisms responsible for such interaction are also discussed here.
Highlights
Melatonin: A Universal and Ubiquitous MoleculeChemically N-acetyl-5-methoxytryptamine, was first isolated and further characterized by Lerner and co-workers in the late 1950s [1,2]
Melatonin, N-acetyl-5-methoxytryptamine, is an indole mainly synthesized from tryptophan in the pineal gland and secreted exclusively during the night in all the animals reported to date
Thanks to the use of RIA and more recently to high-performance liquid chromatography (HPLC) [30,37], the production of the indole has been accurately assayed in several tissues and organs including the retina, Harderian glands, gut, testis or skin, among many others, but these local productions do not seem to contribute to the nocturnal serum levels [38]
Summary
Chemically N-acetyl-5-methoxytryptamine, was first isolated and further characterized by Lerner and co-workers in the late 1950s [1,2]. The Harderian gland was found to demonstrate an immunopositive reaction to melatonin [29], corroborating the findings mentioned above In all these studies the demonstration included non-analytical detection strategies, but rather was based on the immunohistochemical detection of either synthetic enzymes (AANAT/ASMT) or melatonin itself. Thanks to the use of RIA and more recently to high-performance liquid chromatography (HPLC) [30,37], the production of the indole has been accurately assayed in several tissues and organs including the retina, Harderian glands, gut, testis or skin, among many others, but these local productions do not seem to contribute to the nocturnal serum levels [38]. These melatonin metabolite reactions might be of importance in protecting those tissues/organs that act as barriers in the organism, e.g., skin or gut, where melatonin is produced in significant quantitites [106]
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