Hypothalamic Circuits Responsive to Ghrelin: Regulation by Leptin and Insulin

Since its discovery in 1999 (Kojima et al., 1999), ghrelin has emerged as a potentially important circulating hunger-inducing peptide (Wren et al., 2001a; Cummings et al., 2001). It was isolated from the oxyntic glands of the rat stomach (Kojima et al., 1999) and this appears to be the major source of circulating ghrelin as levels are reduced by 80% following gastrectomy (Dordonville de la Cour et al., 2001). Ghrelin mRNA has also been detected in a number of other organs, including the pituitary (Korbonits et al., 2001), hypothalamus (Kojima et al., 1999), kidney (Mori et al., 2000), bowel (Date et al., 2000) and placenta (Gualillo et al., 2001).