, rather than peripheral orexin receptors appear to be a target more relevant to the chronotherapy against type 2 diabetes. In conclusion, we found that 2-SORA-MK1064 improved sleep, glucose metabolism and inflammation profiles in db/db mice, suggesting
Kanta Kon, Hiroshi Tsuneki, Hisakatsu Ito, Yoshinori Takemura, Kiyofumi Sato, Mitsuaki Yamazaki, Yoko Ishii, Masakiyo Sasahara, Assaf Rudich, Takahiro Maeda, Tsutomu Wada and Toshiyasu Sasaoka
Marianna Minnetti, Valeria Hasenmajer, Riccardo Pofi, Mary Anna Venneri, Krystallenia I Alexandraki and Andrea M Isidori
The circadian rhythm derives from the integration of many signals that shape the expression of clock-related genes in a 24-hour cycle. Biological tasks, including cell proliferation, differentiation, energy storage and immune regulation, are preferentially confined to specific periods. A gating system, supervised by the central and peripheral clocks, coordinates the endogenous and exogenous signals and prepares for transition to activities confined to periods of light or darkness. The fluctuations of cortisol and its receptor are crucial in modulating these signals. Glucocorticoids and the autonomous nervous system act as a bridge between the suprachiasmatic master clock and almost all peripheral clocks. Additional peripheral synchronizing mechanisms including metabolic fluxes and cytokines stabilize the network. The pacemaker is amplified by peaks and troughs in cortisol and their response to food, activity, and inflammation. However, when the glucocorticoid exposure pattern becomes chronically flattened at high (as in Cushing’s syndrome) or low (as in adrenal insufficiency) levels, the system fails. While endocrinologists are well aware of cortisol rhythm, too little attention has been given to interventions aimed at restoring physiological cortisol fluctuations in adrenal disorders. However, acting on glucocorticoid levels may not be the only way to restore clock-related activities. First, a counterregulatory mechanism on the glucocorticoid receptor itself controls signal transduction, and second, melatonin and/or metabolically active drugs and nutrients could also be used to modulate the clock. All these aspects are described herein, providing some insights into the emerging role of chronopharmacology, focusing on glucocorticoid excess and deficiency disorders.
Cátia F Gonçalves and Qing-Jun Meng
in skeletal metabolism and pathophysiology of diseases. Finally, we provide an overview of the latest advances in chronotherapy and other translational aspects of circadian biology and discuss how these can be used to improve existing therapies and
Michael Hastings, John S O’Neill and Elizabeth S Maywood
et al . 2005 ). In a clinical context, these interactions are open to exploitation by seeking to time the delivery of cytotoxic therapies to coincide with points of vulnerability within tumour cells (chronotherapy) but such regimes also need to