{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:57:17Z","timestamp":1783573037678,"version":"3.55.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:p>Glucagon\u2010like peptide 1 (GLP\u20101) receptor agonists (GLP\u20101\u2010RAs) act on multiple tissues, in addition to the pancreas. Recent studies suggest that GLP\u20101\u2010RAs act on liver and adipose tissue to reduce insulin resistance (IR). Thus, we evaluated the acute effects of exenatide (EX) on hepatic (Hep\u2010IR) and adipose (Adipo\u2010IR) insulin resistance and glucose uptake. Fifteen male subjects (age = 56 \u00b1 8 years; body mass index = 29 \u00b1 1 kg\/m<jats:sup>2<\/jats:sup>; A1c = 5.7 \u00b1 0.1%) were studied on two occasions, with a double\u2010blind subcutaneous injection of EX (5 \u03bcg) or placebo (PLC) 30 minutes before a 75\u2010g oral glucose tolerance test (OGTT). During OGTT, we measured hepatic (HGU) and adipose tissue (ATGU) glucose uptake with [<jats:sup>18<\/jats:sup>F]2\u2010fluoro\u20102\u2010deoxy\u2010D\u2010glucose\/positron emission tomography, lipolysis (RaGly) with [U\u2010<jats:sup>2<\/jats:sup>H<jats:sub>5<\/jats:sub>]\u2010glycerol, oral glucose absorption (RaO) with [U\u2010<jats:sup>13<\/jats:sup>C<jats:sub>6<\/jats:sub>]\u2010glucose, and hepatic glucose production (EGP) with [6,6\u2010<jats:sup>2<\/jats:sup>H<jats:sub>2<\/jats:sub>]\u2010glucose. Adipo\u2010IR and Hep\u2010IR were calculated as (FFA<jats:sub>0\u2010120min<\/jats:sub>) \u00d7 (Ins<jats:sub>0\u2010120min<\/jats:sub>) and (EGP<jats:sub>0\u2010120min<\/jats:sub>) \u00d7 (Ins<jats:sub>0\u2010120min<\/jats:sub>), respectively. EX reduced RaO, resulting in reduced plasma glucose and insulin concentration from 0 to 120 minutes postglucose ingestion. EX decreased Hep\u2010IR (197 \u00b1 28 to 130 \u00b1 37; <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.02) and increased HGU of orally administered glucose (23 \u00b1 4 to 232 \u00b1 89 [\u03bcmol\/min\/L]\/[\u03bcmol\/min\/kg]; <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.003) despite lower insulin (23 \u00b1 5 vs. 41 \u00b1 5 mU\/L; <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.02). EX enhanced insulin suppression of RaGly by decreasing Adipo\u2010IR (23 \u00b1 4 to 13 \u00b1 3; <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.009). No significant effect of insulin was observed on ATGU (EX = 1.16 \u00b1 0.15 vs. PLC = 1.36 \u00b1 0.13 [\u03bcmol\/min\/L]\/[\u03bcmol\/min\/kg]). <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Acute EX administration (1) improves Hep\u2010IR, decreases EGP, and enhances HGU and (2) reduces Adipo\u2010IR, improves the antilipolytic effect of insulin, and reduces plasma free fatty acid levels during OGTT. (H<jats:sc>epatology<\/jats:sc> 2016;64:2028\u20102037).<\/jats:p>","DOI":"10.1002\/hep.28827","type":"journal-article","created":{"date-parts":[[2016,9,17]],"date-time":"2016-09-17T15:19:13Z","timestamp":1474125553000},"page":"2028-2037","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":93,"title":["Exenatide improves both hepatic and adipose tissue insulin resistance: A dynamic positron emission tomography study"],"prefix":"10.1097","volume":"64","author":[{"given":"Amalia","family":"Gastaldelli","sequence":"first","affiliation":[{"name":"University of Texas Health Science Center at San Antonio,San Antonio,TX"},{"name":"Institute of Clinical Physiology,Pisa,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melania","family":"Gaggini","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology,Pisa,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Daniele","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at San Antonio,San Antonio,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demetrio","family":"Ciociaro","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology,Pisa,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Cersosimo","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at San Antonio,San Antonio,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devjit","family":"Tripathy","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at San Antonio,San Antonio,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis","family":"Triplitt","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at San Antonio,San Antonio,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Fox","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at San Antonio,San Antonio,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Musi","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at San Antonio,San Antonio,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"DeFronzo","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at San Antonio,San Antonio,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Iozzo","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology,Pisa,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,11,18]]},"reference":[{"key":"hep28827-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s00125-005-0107-1","article-title":"Glucagon\u2010like peptide\u20101: from extract to agent. 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