For decades, the influence of the pineal gland on carbohydrate metabolism has been investigated. However, contradictory results have not yet elucidated the role played by melatonin in carbohydrate homeostasis. In our recent studies, we have contributed to characterize the role of the pineal gland as a modulator of carbohydrate metabolism. In addition, based on present-day knowledge, we have demonstrated the steps of insulin action mechanism involved in this modulation. Our studies reveal that pinealectomy causes a condition of obesity-free insulin resistance. The maximum uptake of 2-deoxi-glucose prompted by insulin in isolated adipocytes is diminished, without however changing the insulin capacity to bind to its receptor, and to stimulate the phosphorilation of intracellular substrates represented by pp 185. Conversely, in several insulin-sensitive tissues, our studies detected a decrease in the amount of glucose transporter protein GLUT4, and a decrease in GLUT4 mRNA in only some of these tissues, suggesting a tissue-specific regulation. Additionally, it was demonstrated that the pineal gland regulation influences carbohydrate metabolism through melatonin, by our demonstration that the hormone increased insulin sensitivity of isolated adipocytes, and that melatonin replacement therapy restored the amount of GLUT4 in white adipose tissue. In summary, the studies reported here evidence an important role played by the pineal gland in the modulation of carbohydrate homeostasis. This regulation seems to be melatonin-dependent and can be described, so far, as an increase in tissue sensitivity to insulin, which involves changes in GLUT4 gene expression.
Melatonin; Pineal gland; Carbohydrate metabolism; Glycemic homeostasis; GLUT4
