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Carnosine, the substrate of the enzyme encoded by this gene, is considered renoprotective and could possibly be used to treat diabetic nephropathy (DN). In this study, we examined the effect of carnosine treatment <jats:italic>in vivo<\/jats:italic> in BTBR (Black and Tan, BRachyuric) <jats:italic>ob\/ob<\/jats:italic> mice, a type 2 diabetes model which develops a phenotype that closely resembles advanced human DN. Treatment of BTBR <jats:italic>ob\/ob<\/jats:italic> mice with 4\u2009mM carnosine for 18 weeks reduced plasma glucose and HbA1c, concomitant with elevated insulin and C-peptide levels. Also, albuminuria and kidney weights were reduced in carnosine-treated mice, which showed less glomerular hypertrophy due to a decrease in the surface area of Bowman\u2019s capsule and space. Carnosine treatment restored the glomerular ultrastructure without affecting podocyte number, resulted in a modified molecular composition of the expanded mesangial matrix and led to the formation of carnosine-acrolein adducts. Our results demonstrate that treatment with carnosine improves glucose metabolism, albuminuria and pathology in BTBR <jats:italic>ob\/ob<\/jats:italic> mice. Hence, carnosine could be a novel therapeutic strategy to treat patients with DN and\/or be used to prevent DN in patients with diabetes.<\/jats:p>","DOI":"10.1038\/srep44492","type":"journal-article","created":{"date-parts":[[2017,3,10]],"date-time":"2017-03-10T10:29:37Z","timestamp":1489141777000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":118,"title":["Carnosine Attenuates the Development of both Type 2 Diabetes and Diabetic Nephropathy in BTBR ob\/ob Mice"],"prefix":"10.1038","volume":"7","author":[{"given":"Thomas","family":"Albrecht","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike","family":"Schilperoort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana D.","family":"Braun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiedong","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego O.","family":"Pastene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard K.","family":"Kr\u00e4mer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannes","family":"K\u00f6ppel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Baelde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile","family":"de Heer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Anna Altomare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Regazzoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Denisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Aldini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"van den Born","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benito A.","family":"Yard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibylle J.","family":"Hauske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,10]]},"reference":[{"key":"BFsrep44492_CR1","doi-asserted-by":"crossref","first-page":"164","DOI":"10.2337\/diacare.28.1.164","volume":"28","author":"JL Gross","year":"2005","unstructured":"Gross, J. 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