Vitam Horm
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The hypothalamic peptide orexin plays a role in many physiological systems including feeding behavior, sleep-wakefulness, reward system, stress, and nociception. In addition, it is now clear that orexin is involved in the central regulation of cardiorespiratory function. Here, we review the cardiorespiratory effects elicited by central orexin and consider the physiological role of this peptide in central cardiorespiratory control in normal and pathophysiological states. ⋯ Orexin neurons stimulate respiration and are sensitive to changes in pH. Orexin knockout mice have apnoeic episodes in sleep. Therefore, orexin may be a potentially important therapeutic target for the treatment of cardiorespiratory disorders.
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Orexin, also called hypocretin, is a neuropeptide produced in neurons sparsely distributed in the lateral hypothalamic area. Orexin exhibits its physiological effects after binding two G-protein-coupled receptors, orexin 1 receptor and orexin 2 receptor. ⋯ However, growing evidence also suggests that orexin affects the function of peripheral tissues via direct activation of orexin receptors or through activation of autonomic nervous or endocrine systems. In this review, we discuss the physiological roles of orexin not only in the central nervous system but also in the peripheral tissues.
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Vitamin D plays a major role in bone mineral density and calcium homeostasis. Apart from its classical action, the active form of vitamin D [1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))] influences the innate and adaptive immune functions through vitamin D receptor (VDR) that are present in various cells of the immune system. Vitamin D deficiencies have been associated with development of tuberculosis (TB) disease, caused by Mycobacterium tuberculosis. ⋯ VDR gene polymorphisms regulate the immunomodulatory effect of vitamin D(3) and are associated with faster sputum conversion during anti-TB treatment. The emerging evidences regarding immunomodulatory properties of vitamin D(3) have rekindled interest in vitamin D as an adjunct to anti-TB therapy. The current review explains the important potential application of vitamin D in enhancing the innate immunity to TB and the role of VDR gene variants on anti-TB treatment.
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Review
GPR119 agonists for the potential treatment of type 2 diabetes and related metabolic disorders.
Type 2 diabetes (T2D) has reached epidemic proportions, and there is an unmet medical need for orally effective agents that regulate glucose homeostasis. GPR119, a class-A (rhodopsin-like) G protein-coupled receptor expressed primarily in the pancreas and gastrointestinal tract, has attracted considerable interest as a T2D drug target in recent years. ⋯ Oral administration of small molecule GPR119 agonists has been shown to improve glucose tolerance in both rodents and humans. This review summarizes the research leading to the identification of GPR119 as a potential drug target for T2D and related metabolic disorders, and provides an overview of the recent progress made in the discovery of orally active GPR119 agonists.
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The endocannabinoid system has been proposed to modulate neuronal functions involved in distinct types of defensive reactions, possibly counteracting the harmful consequences of stressful stimuli. However, the precise brain sites for this action remain to be further explored. This chapter summarizes the data about the role of the endocannabinoid system in the processing of conditioned fear as well as the potential neural subtract for its actions.