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Specifically, <jats:italic>ABCC5<\/jats:italic> gene overexpression was shown to be strongly associated with increased visceral fat mass and reduced peripheral insulin sensitivity. Currently, the role of ABCC5 in diabetes and obesity is unknown. This study reports the metabolic phenotyping of a global <jats:italic>Abcc5<\/jats:italic> knockout mouse.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A global <jats:italic>Abcc5<jats:sup>\u2010\/\u2010<\/jats:sup><\/jats:italic> mouse was generated by CRISPR\/Cas9. Fat mass was determined by weekly EchoMRI and fat pads were dissected and weighed at week 18. Glucose homeostasis was ascertained by an oral glucose tolerance test, intraperitoneal glucose tolerance test, and intraperitoneal insulin tolerance test. Energy expenditure and locomotor activity were measured using PhenoMaster cages. Glucagon\u2010like peptide 1 (GLP\u20101) levels in plasma, primary gut cell cultures, and GLUTag cells were determined by enzyme\u2010linked immunosorbent assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Abcc5<jats:sup>\u2010\/\u2010<\/jats:sup><\/jats:italic> mice had decreased fat mass and increased plasma levels of GLP\u20101, and they were more insulin sensitive and more active. Recombinant overexpression of ABCC5 protein in GLUTag cells decreased GLP\u20101 release.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ABCC5 protein expression levels are inversely related to fat mass and appear to play a role in the regulation of GLP\u20101 secretion from enteroendocrine cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/oby.22521","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T07:12:04Z","timestamp":1563952324000},"page":"1292-1304","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["<i>Abcc5<\/i> Knockout Mice Have Lower Fat Mass and Increased Levels of Circulating GLP\u20101"],"prefix":"10.1002","volume":"27","author":[{"given":"Malgorzata","family":"Cyranka","sequence":"first","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics University of Oxford Oxford 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