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タイトル: | Increase of Total Nephron Albumin Filtration and Reabsorption in Diabetic Nephropathy |
著者: | Mori, Keita P. Yokoi, Hideki Kasahara, Masato Imamaki, Hirotaka Ishii, Akira Kuwabara, Takashige Koga, Kenichi Kato, Yukiko Toda, Naohiro Ohno, Shoko Kuwahara, Koichiro Endo, Tomomi Nakao, Kazuwa Yanagita, Motoko Mukoyama, Masashi Mori, Kiyoshi |
著者名の別形: | 森, 慶太 森, 潔 |
発行日: | 6-Jul-2016 |
出版者: | American Society of Nephrology (ASN) |
誌名: | Journal of the American Society of Nephrology |
抄録: | There is a hot debate concerning actual amount of albumin filtered through glomeruli and reabsorbed at proximal tubules in normal kidneys and diabetic conditions. To overcome current technical problems, we generated a drug-inducible megalin knockout mouse line, megalin(lox/lox);Ndrg1-CreER[T2] (or iMegKO), whose protein reabsorption can be shut off anytime by tamoxifen (Tam). After Tam administration, renal megalin protein expression was reduced by 92% compared to wild-type C57BL/6J mice, and renal reabsorption of intravenously-injected retinol binding protein was almost completely abrogated. Urinary albumin excretion increased to 175 μg/day (0.460 mg/mg-creatinine), suggesting that this was the amount of total nephron albumin filtration. Glomerular sieving coefficient of albumin was 1.7 x 10[-5]. By comparing streptozotocin-induced, Tam-treated, diabetic STZ;iMegKO mice with non-STZ;iMegKO mice, we estimated that daily albumin filtration was increased by 1.9-fold, reabsorption was increased by 1.8-fold, and reabsorption efficiency was reduced to 86% by development of diabetes (versus 96% in control). Such abnormalities were well normalized after insulin treatment. Another type 1 diabetic model of Akita;iMegKO mice showed equivalent results. This study reveals actual values and changes of albumin filtration and reabsorption in early diabetic nephropathy, bringing new insights into our understanding of renal albumin dynamics in hyperfiltration status of diabetic nephropathy |
著作権等: | This is the accepted version of the article, which has been published in final form at http://jasn.asnjournals.org/content/early/2016/07/05/ASN.2015101168. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/216097 |
DOI(出版社版): | 10.1681/ASN.2015101168 |
PubMed ID: | 27382987 |
出現コレクション: | 学術雑誌掲載論文等 |
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