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Insulin signaling in the brain is catabolic, reducing food intake. We hypothesized that DET reduces weight gain, relative to other insulins, owing to increased transport into the central nervous system and\/or increased catabolic action within the brain. Transport of DET and NPH insulin into the cerebrospinal fluid (CSF) was compared over several hours and after the administration of different doses peripherally in rats. DET and NPH had comparable saturable, receptor-mediated transport into the CSF. CSF insulin remained elevated significantly longer after intraperitoneal DET than after NPH. When administered acutely into the 3rd cerebral ventricle, both DET and NPH insulin reduced food intake and body weight at 24 h, and both food intake and body weight remained lower after DET than after NPH after 48 h. In direct comparison with another long-acting insulin, insulin glargine (GLAR), DET led to more prolonged increases in CSF insulin despite a shorter plasma half-life in both rats and mice. Additionally, peripheral DET administration reduced weight gain and increased CSF insulin compared with saline or GLAR in mice. Overall, these data support the hypothesis that DET has distinct effects on energy balance through enhanced and prolonged centrally mediated reduction of food intake.<\/jats:p>","DOI":"10.2337\/db14-1364","type":"journal-article","created":{"date-parts":[[2015,2,10]],"date-time":"2015-02-10T04:02:03Z","timestamp":1423540923000},"page":"2457-2466","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":31,"title":["Insulin Detemir Is Transported From Blood to Cerebrospinal Fluid and Has Prolonged Central Anorectic Action Relative to NPH Insulin"],"prefix":"10.2337","volume":"64","author":[{"given":"Denovan P.","family":"Begg","sequence":"first","affiliation":[{"name":"Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH"},{"name":"School of Psychology, UNSW Australia, Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron A.","family":"May","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joram D.","family":"Mul","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH"},{"name":"Joslin Diabetes Center, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"D\u2019Alessio","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH"},{"name":"Department of Medicine, Duke University, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy J.","family":"Seeley","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH"},{"name":"Department of Surgery, University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Woods","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2015,2,9]]},"reference":[{"key":"2022031212294504200_B1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1152\/advan.00167.2012","article-title":"Interactions between the central nervous system and pancreatic islet secretions: a historical perspective","volume":"37","author":"Begg","year":"2013","journal-title":"Adv Physiol Educ"},{"key":"2022031212294504200_B2","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1210\/endo-113-5-1818","article-title":"Immunocytochemical detection of insulin in rat hypothalamus and its possible uptake from cerebrospinal fluid","volume":"113","author":"Baskin","year":"1983","journal-title":"Endocrinology"},{"key":"2022031212294504200_B3","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/282623a0","article-title":"Insulin binds to brain blood vessels in vivo","volume":"282","author":"van Houten","year":"1979","journal-title":"Nature"},{"key":"2022031212294504200_B4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ejphar.2004.02.040","article-title":"The source of cerebral insulin","volume":"490","author":"Banks","year":"2004","journal-title":"Eur J Pharmacol"},{"key":"2022031212294504200_B5","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1161\/HYPERTENSIONAHA.110.160671","article-title":"Sympathetic response to insulin is mediated by melanocortin 3\/4 receptors in the hypothalamic paraventricular nucleus","volume":"57","author":"Ward","year":"2011","journal-title":"Hypertension"},{"key":"2022031212294504200_B6","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.2337\/db08-1039","article-title":"Hypothalamic reactive oxygen species are required for insulin-induced food intake inhibition: an NADPH oxidase-dependent mechanism","volume":"58","author":"Jaillard","year":"2009","journal-title":"Diabetes"},{"key":"2022031212294504200_B7","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.bandc.2007.01.002","article-title":"Intrahippocampal insulin improves memory in a passive-avoidance task in male wistar rats","volume":"64","author":"Babri","year":"2007","journal-title":"Brain Cogn"},{"key":"2022031212294504200_B8","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1172\/JCI116773","article-title":"Saturable transport of insulin from plasma into the central nervous system of dogs in vivo. 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