Ghrelin (human) was isolated from the gut of both human and rat as the endogenous ligand of the growth hormone secretagogue receptor (GHS-R), and has an effection on the activity of arcute neurones with a much stronger affinity (IC50, 0.3×10-9M) than GHSR antagonist (D-Lys3)-GHRP-6 (IC50, 0.9×10-6M). The highest levels of ghrelin are secreted from the X/A - like cells of the oxyntic glands located in the gastric fundus, with lower levels widely distributed throughout the body. Ghrelin is secreted direct into the local gastric circulation and transported to the brain directly, requiring it to either cross the blood-brain barrier via a saturated transport system or via the blood stream to enter areas of the brain that are not protected by the blood-brain barrier. Ghrelin modulates the hypothalamic arcuate nucleus, in an indirect manner, via activation of the vagus nerve and brain stem nuclei . Ghrelin has a homeostatic role that encompasses multiple areas of the body, with actions that include downregulation of brown adipose tissue thermogenesis , modulation of non-hypothalamic brain regions producing an increased taste sensation and stimulation of gastric emptying and motility. The actions of ghrelin may contribute to the development of T2DM and obesity .