{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T18:29:30Z","timestamp":1793471370107,"version":"4.5.0"},"reference-count":46,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:p>Glucagon-like peptide-1 (GLP-1) improves insulin sensitivity in humans and rodents. It is currently unknown to what extent the (metabolic) effects of GLP-1 treatment are mediated by central GLP-1 receptors. We studied the impact of central GLP-1 receptor (GLP-1R) antagonism on the metabolic effects of peripheral GLP-1 administration in mice. High-fat-fed insulin-resistant C57Bl\/6 mice were treated with continuous subcutaneous infusion of GLP-1 or saline (PBS) for 2 wk, whereas the GLP-1R antagonist exendin-9 (EX-9) and cerebrospinal fluid (CSF) were simultaneously infused in the left lateral cerebral ventricle (icv). Glucose and glycerol turnover were determined during a hyperinsulinemic euglycemic clamp. VLDL-triglyceride (VLDL-TG) production was determined in hyperinsulinemic conditions. Our data show that the rate of glucose infusion necessary to maintain euglycemia was significantly increased by GLP-1. Simultaneous icv infusion of EX-9 diminished this effect by 62%. The capacities of insulin to stimulate glucose disposal and inhibit glucose production were reinforced by GLP-1. Simultaneous icv infusion of EX-9 significantly diminished the latter effect. Central GLP-1R antagonism alone did not affect glucose metabolism. Also, GLP-1 treatment reinforced the inhibitory action of insulin on VLDL-TG production. In conclusion, peripheral administration of GLP-1 reinforces the ability of insulin to suppress endogenous glucose and VLDL-TG production (but not lipolysis) and boosts its capacity to stimulate glucose disposal in high-fat-fed C57Bl\/6 mice. Activation of central GLP-1Rs contributes substantially to the inhibition of endogenous glucose production by GLP-1 treatment in this animal model.<\/jats:p>","DOI":"10.1152\/ajpendo.00191.2010","type":"journal-article","created":{"date-parts":[[2010,6,8]],"date-time":"2010-06-08T20:22:05Z","timestamp":1276028525000},"page":"E318-E324","source":"Crossref","is-referenced-by-count":74,"title":["GLP-1 treatment reduces endogenous insulin resistance via activation of central GLP-1 receptors in mice fed a high-fat diet"],"prefix":"10.1152","volume":"299","author":[{"given":"Edwin T.","family":"Parlevliet","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith E.","family":"de Leeuw van Weenen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes A.","family":"Romijn","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanno","family":"Pijl","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116066"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.2.252"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.02.06.db05-0686"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2006.1855"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.7.8770921"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.09.033"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2007.04.003"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-1349"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1995.tb00650.x"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.19.8.843"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.490160110"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-8051(98)00121-8"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(87)81430-8"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(03)00174-8"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902710405"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.19.11.1200"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:18:1-2:07"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0180"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25764"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-006-0439-5"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)91194-9"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(96)00434-4"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.23.2.0461"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02580-4"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-0126-y"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.3.654"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990111)403:2<261::AID-CNE8>3.0.CO;2-5"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5977-08.2009"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.144154"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1021\/bi049887s"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00024.2003"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00303.2004"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1824"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2874"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.059741"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.K08E-091"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.2337\/diab.37.9.1163"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.47.11.1687"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/379069a0"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.10.2529"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1210\/endo.132.5.7682936"},{"key":"B43","unstructured":"Wolfe RR , Chinkes DL.\n                      Isotope Tracers in Metabolic Research: Principle & Practice of Kinetic Analysis\n                      . New York: Wiley, 2004, p. 222\u2013234."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-978985"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.5.1026"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)07952-7"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-007-0737-6"}],"container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpendo.00191.2010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T16:21:24Z","timestamp":1567959684000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpendo.00191.2010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,8]]},"references-count":46,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2010,8]]}},"alternative-id":["10.1152\/ajpendo.00191.2010"],"URL":"https:\/\/doi.org\/10.1152\/ajpendo.00191.2010","relation":{},"ISSN":["0193-1849","1522-1555"],"issn-type":[{"value":"0193-1849","type":"print"},{"value":"1522-1555","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,8]]}}}