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The influence of serum CN1 expression on obesity, hyperglycemia, and renal impairment was assessed. We also studied if aggravation of renal impairment in hCN1 TG BTBR<jats:sup>Ob\/Ob<\/jats:sup> mice leads to changes in the renal transcriptome as compared with wild-type BTBR<jats:sup>Ob\/Ob<\/jats:sup> mice.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>hCN1 was detected in the serum and urine of mice from two different hCN1 TG lines. The transgene was expressed in the liver but not in the kidney. High CN1 expression was associated with low plasma and renal carnosine concentrations, even after oral carnosine supplementation. Obese hCN1 transgenic BTBR<jats:sup>Ob\/Ob<\/jats:sup> mice displayed significantly higher levels of glycated hemoglobin, glycosuria, proteinuria, and increased albumin-creatinine ratios (1104 \u00b1 696 vs 492.1 \u00b1 282.2 \u03bcg\/mg) accompanied by an increased glomerular tuft area and renal corpuscle size. Gene-expression profiling of renal tissue disclosed hierarchical clustering between BTBR<jats:sup>Ob\/Wt<\/jats:sup>, BTBR<jats:sup>Ob\/Ob,<\/jats:sup> and hCN1 BTBR<jats:sup>Ob\/Ob<\/jats:sup> mice. Along with aggravation of the DKD phenotype, 26 altered genes have been found in obese hCN1 transgenic mice; among them claudin-1, thrombospondin-1, nephronectin, and peroxisome proliferator\u2013activated receptor-alpha have been reported to play essential roles in DKD.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our data support a role for serum carnosinase 1 in the progression of DKD. Whether this is mainly attributed to the changes in renal carnosine concentrations warrants further studies.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Key messages<\/jats:title>\n<jats:p><jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p>Increased carnosinase 1 (CN1) is associated with diabetic kidney disease (DKD).<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>BTBR<jats:sup>Ob\/Ob<\/jats:sup> mice with human CN1 develop a more aggravated DKD phenotype.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Microarray revealed alterations by CN1 which are not altered by hyperglycemia.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>These genes have been described to play essential roles in DKD.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Inhibiting CN1 could be beneficial in DKD.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s00109-020-01957-0","type":"journal-article","created":{"date-parts":[[2020,8,15]],"date-time":"2020-08-15T11:02:42Z","timestamp":1597489362000},"page":"1333-1346","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Human carnosinase 1 overexpression aggravates diabetes and renal impairment in BTBROb\/Ob mice"],"prefix":"10.1007","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9835-8398","authenticated-orcid":false,"given":"Jiedong","family":"Qiu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Albrecht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiqi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sibylle J.","family":"Hauske","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelica","family":"Rodriguez-Ni\u00f1o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinmiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darya","family":"Nosan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego O.","family":"Pastene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Sticht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Delatorre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry","family":"van Goor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Porubsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard K.","family":"Kr\u00e4mer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benito A.","family":"Yard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,8,15]]},"reference":[{"key":"1957_CR1","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.diabres.2017.03.024","volume":"128","author":"K Ogurtsova","year":"2017","unstructured":"Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, Cavan D, Shaw JE, Makaroff LE (2017) IDF diabetes atlas: global estimates for the prevalence of diabetes for 2015 and 2040. 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The experiments were approved by the Regierungspr\u00e4sidium in Karlsruhe, Germany (AZ 35-9185.81\/G-116\/14 and G-108\/13).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}},{"value":"The authors declare that they have no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}