{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T17:34:00Z","timestamp":1771954440320,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,11,8]],"date-time":"2012-11-08T00:00:00Z","timestamp":1352332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study examined the biological properties of a novel GLP\u20101 peptide, (Val<jats:sup>8<\/jats:sup>)GLP\u20101\u2010Glu\u2010PAL, engineered with an Ala<jats:sup>8<\/jats:sup>\u2192Val<jats:sup>8<\/jats:sup> substitution and additional incorporation of a C<jats:sub>16<\/jats:sub> fatty acid moiety at Lys<jats:sup>26<\/jats:sup> via a glutamic acid linker. GLP\u20101 underwent 75\u2009% degradation by DPP\u2010IV over 8\u2005h, whereas (Val<jats:sup>8<\/jats:sup>)GLP\u20101 and (Val<jats:sup>8<\/jats:sup>)GLP\u20101\u2010Glu\u2010PAL remained intact. All GLP\u20101 peptides significantly stimulated insulin secretion at 5.6\u2005m<jats:sc>M<\/jats:sc> (1.3\u2010 to 4.9\u2010fold, <jats:italic>p<\/jats:italic>&lt;0.01 to <jats:italic>p<\/jats:italic>&lt;0.001) and 16.7\u2005m<jats:sc>M<\/jats:sc> glucose (1.5\u2010 to 2.3\u2010fold, <jats:italic>p<\/jats:italic>&lt;0.001). At higher concentrations (Val<jats:sup>8<\/jats:sup>)GLP\u20101\u2010Glu\u2010PAL was significantly more potent at stimulating insulin secretion (1.2\u2010 to 1.3\u2010fold, <jats:italic>p<\/jats:italic>&lt;0.05). In high\u2010fat\u2010fed mice, all GLP\u20101 peptides significantly lowered plasma glucose concentrations (41\u201366\u2009% decrease, <jats:italic>p<\/jats:italic>&lt;0.05 to <jats:italic>p<\/jats:italic>&lt;0.001), with (Val<jats:sup>8<\/jats:sup>)GLP\u20101\u2010Glu\u2010PAL eliciting protracted glucose\u2010lowering actions (32\u201359\u2009% decrease, <jats:italic>p<\/jats:italic>&lt;0.05 to <jats:italic>p<\/jats:italic>&lt;0.01) when administered 8\u2005h prior to a glucose load. Twice\u2010daily administration of (Val<jats:sup>8<\/jats:sup>)GLP\u20101\u2010Glu\u2010PAL in high\u2010fat\u2010fed mice for 21 days had no effect on bodyweight or food intake, but significantly lowered non\u2010fasting plasma glucose (43\u201346\u2009% decrease, <jats:italic>p<\/jats:italic>&lt;0.05). (Val<jats:sup>8<\/jats:sup>)GLP\u20101\u2010Glu\u2010PAL markedly decreased glycemic excursion following intraperitoneal glucose (32\u201348\u2009% decrease, <jats:italic>p<\/jats:italic>&lt;0.05), enhanced insulin response to glucose (2\u2010 to 2.3\u2010fold, <jats:italic>p<\/jats:italic>&lt;0.05 to <jats:italic>p<\/jats:italic>&lt;0.01), and improved insulin sensitivity (25\u201338\u2009% decrease in plasma glucose, <jats:italic>p<\/jats:italic>&lt;0.05). O<jats:sub>2<\/jats:sub> consumption, CO<jats:sub>2<\/jats:sub> production, RER, and energy expenditure were not altered by (Val<jats:sup>8<\/jats:sup>)GLP\u20101\u2010Glu\u2010PAL therapy. Treatment with (Val<jats:sup>8<\/jats:sup>)GLP\u20101\u2010Glu\u2010PAL resulted in a significant increase in BrdU\u2010positive cells (1.3\u2010fold, <jats:italic>p<\/jats:italic>&lt;0.05) in the granule cell layer of the dentate gyrus. These data demonstrate that (Val<jats:sup>8<\/jats:sup>)GLP\u20101\u2010Glu\u2010PAL is a long\u2010acting GLP\u20101 peptide that significantly improves hippocampal neurogenesis, glucose homeostasis, and insulin secretion in high\u2010fat\u2010fed mice.<\/jats:p>","DOI":"10.1002\/cmdc.201200409","type":"journal-article","created":{"date-parts":[[2012,11,8]],"date-time":"2012-11-08T08:02:58Z","timestamp":1352361778000},"page":"595-602","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["(Val<sup>8<\/sup>)GLP\u20101\u2010Glu\u2010PAL: a GLP\u20101 Agonist That Improves Hippocampal Neurogenesis, Glucose Homeostasis, and \u03b2\u2010Cell Function in High\u2010Fat\u2010Fed Mice"],"prefix":"10.1002","volume":"8","author":[{"given":"Rachael","family":"Lennox","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Porter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter R.","family":"Flatt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor A.","family":"Gault","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,11,8]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1900\/RDS.2011.8.293"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.130.1.1309325"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)91194-9"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1999.277.3.R910"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1999.276.5.R1541"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e32832fbf14"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-381517-0.00013-8"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2010.59"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2010.01259.x"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.02.014"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0529-11.2011"},{"key":"e_1_2_7_12_2","unstructured":"W.\u2005D. Porter P.\u2005R. Flatt C. H\u00f6lscher V.\u2005A. Gault Int. J. Obes. (Lond.)2012 DOI:."},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.136.8.7628397"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2007.09.003"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.097824"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.03.025"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.08.028"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.11.005"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.07.029"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3120725"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm9909645"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.2174\/156720512799015064"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1002190"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.31.9.896"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2004.035"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2008.11.018"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.729"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61375-1"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2008.11.007"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-007-0710-4"},{"key":"e_1_2_7_31_2","first-page":"1205","volume":"19","author":"Li H.","year":"2010","journal-title":"Neurosci. Lett."},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22565"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1667\/RR3206"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.10.009"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0782-06.2006"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-13-33"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm049262s"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.8.1132"},{"key":"e_1_2_7_39_2","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1523\/JNEUROSCI.22-02-00515.2002","volume":"22","author":"Bondolfi L.","year":"2002","journal-title":"J. Neurosci."},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(71)90332-9"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00252768"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcmdc.201200409","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.201200409","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T11:42:24Z","timestamp":1760269344000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.201200409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,8]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1002\/cmdc.201200409"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.201200409","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,8]]},"assertion":[{"value":"2012-09-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-11-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}