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Moreover, Pax6m\/+ mice showed increased food intake compared with control mice, although they were resistant to diet-induced fat accumulation. Indeed, levels of circulating GLP-1 and intestinal transcription of Gcg\/Proglucagon were dramatically reduced in Pax6m\/+ mice. Mutated Pax6 also failed to activate the Gcg\/Proglucagon promoter by in vitro transfection assay. Finally, administering the GLP-1 receptor agonist exendin-4 to Pax6m\/+ mice largely reversed their abnormal food intake, glycemic excursion, and insulin secretion. Our studies suggested that disruption of metabolic homeostasis mainly caused by Pax6 haploinsufficiency was mainly mediated by down-regulation of GLP-1. Administration of exendin-4 may be a useful therapy in humans with a similar mutation.<\/jats:p>","DOI":"10.1210\/en.2008-1006","type":"journal-article","created":{"date-parts":[[2008,12,31]],"date-time":"2008-12-31T01:34:24Z","timestamp":1230687264000},"page":"2136-2144","source":"Crossref","is-referenced-by-count":32,"title":["Pax6 Haploinsufficiency Causes Abnormal Metabolic Homeostasis by Down-Regulating Glucagon-Like Peptide 1 in Mice"],"prefix":"10.1210","volume":"150","author":[{"given":"Jun","family":"Ding","sequence":"first","affiliation":[{"name":"Model Animal Research Center (J.D., Y.G., J.Z., H.Y., S.G., X.G.), Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Research, Medical School of Nanjing University, Nanjing 210061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gao","sequence":"additional","affiliation":[{"name":"Model Animal Research Center (J.D., Y.G., J.Z., H.Y., S.G., X.G.), Ministry of Education (MOE) 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