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Here, we show that crossing the Y2 receptor knockout mouse (Y2\u2212\/\u2212) onto the ob\/ob background attenuates the increased adiposity, hyperinsulinemia, hyperglycemia, and increased hypothalamo-pituitary-adrenal (HPA) axis activity of ob\/ob mice. Compared with lean controls, ob\/ob mice had elevated expression of NPY and agouti-related protein (AgRP) mRNA in the arcuate nucleus and decreased expression of proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA. Y2 deletion in ob\/ob mice significantly increased the hypothalamic POMC mRNA expression, with no effect on NPY, AgRP, or CART expression. [Y2\u2212\/\u2212ob\/ob] mice were no different from ob\/ob littermates with respect to food intake and body weight, and Y2 receptor deficiency had no beneficial effect on the infertility or the reduced hypothalamo-pituitary-gonadotropic function of ob\/ob mice. These data demonstrate that Y2 receptors mediate the obese type 2 diabetes phenotype of ob\/ob mice, possibly via alterations in melanocortin tonus in the arcuate nucleus and\/or effects on the HPA axis.<\/jats:p>","DOI":"10.2337\/diabetes.51.12.3420","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"3420-3427","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":87,"title":["Y2 Receptor Deletion Attenuates the Type 2 Diabetic Syndrome of <i>ob\/ob<\/i> Mice"],"prefix":"10.2337","volume":"51","author":[{"given":"Amanda","family":"Sainsbury","sequence":"first","affiliation":[{"name":"From the Neurobiology Program, Garvan Institute of Medical Research, St. Vincent\u2019s Hospital, Sydney, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Schwarzer","sequence":"additional","affiliation":[{"name":"From the Neurobiology Program, Garvan Institute of Medical Research, St. Vincent\u2019s Hospital, Sydney, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Couzens","sequence":"additional","affiliation":[{"name":"From the Neurobiology Program, Garvan Institute of Medical Research, St. Vincent\u2019s Hospital, Sydney, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herbert","family":"Herzog","sequence":"additional","affiliation":[{"name":"From the Neurobiology Program, Garvan Institute of Medical Research, St. Vincent\u2019s Hospital, Sydney, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031223235817200_R1","doi-asserted-by":"crossref","unstructured":"Clark JT, Kalra PS, Crowley WR, Kalra SP: Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats. 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