Role of orexins in the central and peripheral regulation of glucose homeostasis: Evidences & mechanisms

Orexins (A & B), neuropeptides of hypothalamic origin, act through G-protein coupled receptors, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R). The wide projection of orexin neurons in the hypothalamic region allows them to interact with the other neurons and regulate food intake, emotional status, sleep wake cycle and energy metabolism. The autonomic nervous system plays an important regulatory role in the energy metabolism as well as glucose homeostasis. Orexin neurons are also under the control of GABAergic neurons. Emerging preclinical as well as clinical research has reported the role of orexins in the glucose homeostasis since orexins are involved in hypothalamic metabolism circuitry and also rely on sensing peripheral metabolic signals such as gut, adipose derived and pancreatic peptides. Apart from the hypothalamic origin, integration and control in various physiological functions, peripheral origin in wide organs, raises the possibility of use of orexins as a therapeutic biomarker in the management of metabolic disorders. The present review focuses the central as well as peripheral roles of orexins in the glucose homeostasis. •Orexins (A & B), neuropeptides of hypothalamic origin are found to be involved in various physiological functions such as sleep wakefulness, emotional well being and energy metabolism.•Apart from the central origin, orexins are also widely distributed in peripheral organs (Adipose tissue, pancreas etc.)•Orexins are found to be involved in lipid and glucose homeostasis centrally as well as peripherally by interacting with other gut, adipose and pancreatic peptides.•Centrally, orexins are involved in glucose homeostasis via regulating the autonomic nervous system.•Peripherally, orexins (Especially Orexin A) are involved in glucose homeostasis via regulating various other peptides and hormones such as insulin, glucagon etc.