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Despite this outstanding discovery at that time, it took more than 140 years before progress started to be made in identifying the underlying mechanisms of brain\u2010mediated control of glucose homeostasis. Technological advances including the generation of brain insulin receptor null mice revealed that insulin action specifically in the central nervous system is required for the regulation of glucose metabolism, particularly in the modulation of hepatic glucose production. Furthermore, it was established that the hormone leptin, known for its role in regulating food intake and body weight, actually exerts its most potent effects on glucose metabolism, and that this function of leptin is mediated centrally. Under certain circumstances, high levels of leptin can replicate the actions of insulin, thus challenging the idea that life without insulin is impossible. Disruptions of central insulin signaling and glucose metabolism not only lead to impairments in whole body glucose homeostasis, they also have other serious consequences, including the development of Alzheimer's disease which is sometimes referred to as type 3 diabetes reflecting its common etiology with type 2 diabetes. \u00a9 2017 American Physiological Society.<jats:italic>Compr Physiol<\/jats:italic>7:471\u2010764, 2017.<\/jats:p>","DOI":"10.1002\/cphy.c160015","type":"other","created":{"date-parts":[[2017,3,16]],"date-time":"2017-03-16T03:23:41Z","timestamp":1489634621000},"page":"741-764","source":"Crossref","is-referenced-by-count":44,"title":["Central Regulation of Glucose Homeostasis"],"prefix":"10.1002","author":[{"given":"Alexander","family":"Tups","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonas","family":"Benzler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenico","family":"Sergi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon R.","family":"Ladyman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynda M.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,16]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1550-8528.1995.tb00493.x"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.09.008"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb01045.x"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.soard.2014.04.005"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9553-3"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20081426"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1964.207.5.1146"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07181"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19990901)57:5<693::AID-JNR11>3.0.CO;2-X"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi962210n"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1185"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2004.05.009"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2004.06.002"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00373626"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200110000-00001"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/13803390490514875"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.04.06.db05-1386"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.19.14563"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.02.030"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.35.4.426"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4022"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.12.3067"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2617-y"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0329"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301193"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000106378"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1746"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20120834"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0093"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59816"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1121"},{"key":"e_1_2_14_33_1","unstructured":"BernardC. 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