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GLP\u20101 has a spectrum of anti\u2010diabetic effects that are of possible utility in the treatment of more severe forms of diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The present study has evaluated the effect of once daily liraglutide injection (25\u00a0nmol\/kg bw) for 15\u00a0days on metabolic control, islet architecture, and islet morphology in C57BL\/KsJ <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Liraglutide had no appreciable effects on body weight, food intake, and non\u2010fasting glucose and insulin concentrations. However, HbA<jats:sub>1c<\/jats:sub> was significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) decreased, and oral glucose tolerance improved in liraglutide treated <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mice. Pancreatic insulin content was increased (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) compared with saline controls, and the ratio of pancreatic insulin to glucagon in liraglutide mice was similar to lean mice. Although liraglutide did not alter islet number or area, the proportion of beta cells per islet was significantly increased (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and alpha cells decreased (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), with normalization of islet architecture. In harmony with this, cell proliferation was significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) augmented and apoptosis reduced (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) in liraglutide treated mice. Expression of pancreatic islet glucose\u2010dependent insulinotropic polypeptide immunoreactivity was observed in lean control and, particularly, liraglutide treated <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mice, whereas control <jats:italic>db<\/jats:italic>\/<jats:italic>db<\/jats:italic> mice exhibited little glucose\u2010dependent insulinotropic polypeptide staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data reveal that stable GLP\u20101 analogues exert important beneficial effects on pancreatic islet architecture and beta\u2010cell turnover, indicating that they may be useful in the treatment of severe forms of diabetes with islet degeneration. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dmrr.2608","type":"journal-article","created":{"date-parts":[[2014,9,24]],"date-time":"2014-09-24T14:20:03Z","timestamp":1411568403000},"page":"248-255","source":"Crossref","is-referenced-by-count":24,"title":["Positive effects of GLP\u20101 receptor activation with liraglutide on pancreatic islet morphology and metabolic control in C57BL\/KsJ <i>db<\/i>\/<i>db<\/i> mice with degenerative diabetes"],"prefix":"10.1002","volume":"31","author":[{"given":"Rachel Charlotte","family":"Moffett","sequence":"first","affiliation":[{"name":"SAAD Centre for Pharmacy and Diabetes University of Ulster  Coleraine Northern Ireland UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Patterson","sequence":"additional","affiliation":[{"name":"SAAD Centre for Pharmacy and Diabetes University of Ulster  Coleraine Northern Ireland UK"},{"name":"School of Life and Health Sciences Glasgow 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