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A recent clinical trial indicated that the dipeptidyl peptidase-4 inhibitor linagliptin prevents the occurrence and progression of albuminuria in patients with type 2 diabetes. Thus, this study aimed to elucidate the molecular mechanism underlying the inhibitory effect of linagliptin on albuminuria in diabetic kidney disease. Methods: Control C57BL/6 mice and diabetic Ins2+/Akita mice were orally administered linagliptin (5 mg/kg/ day) every day for 8 weeks. Results: Compared to control mice, Ins2+/Akita mice had markedly elevated blood glucose and HbA1c levels, but there were no significant changes after linagliptin treatment. Furthermore, albuminuria and urinary 8-OHdG levels were significantly increased and glomerular mesangial area was significantly expanded in Ins2+/Akita mice compared to those in control mice; these changes were ameliorated by linagliptin treatment, which also improved the degradation of glomerular endothelial glycocalyx and enhancement of glomerular permeability of macromolecules. The activity of AMP-activated protein kinase and the expression of guanosine 5\u0027-triphosphate cyclohydrolase I in human glomerular endothelial cells were significantly lower in high glucose conditions and were improved by linagliptin or GLP-1 administration. Discussion: These results together suggest that linagliptin reduced albuminuria in a blood glucose-independent manner via the reduction of oxidative stress and maintenance of the glycocalyx in endothelial cells. 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Dipeptidyl peptidase-4 inhibitor linagliptin reduces urinary albumin excretion through the protection of glomerular endothelial function
https://kwmed.repo.nii.ac.jp/records/3015
https://kwmed.repo.nii.ac.jp/records/30154786c7a0-3512-4ca7-bb43-994c8542db7e
名前 / ファイル | ライセンス | アクション |
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PDF (4.5 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2022-04-01 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Dipeptidyl peptidase-4 inhibitor linagliptin reduces urinary albumin excretion through the protection of glomerular endothelial function | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
KONDO, Megumi
× KONDO, Megumi× KIDOKORO, Kengo× UCHIDA, Atsushi× KADOYA, Hiroyuki× UMENO, Reina× TOKUYAMA, Atsuyuki× WADA, Yoshihisa× NAGASU, Hajime× KANDA, Eiichiro× SASAKI, Tamaki× KASHIHARA, Naoki |
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著者所属(英) | ||||||
en | ||||||
Departments of Nephrology and Hypertension, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Departments of Nephrology and Hypertension, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Departments of Nephrology, Tsukuba Medical Center Hospital | ||||||
著者所属(英) | ||||||
en | ||||||
Departments of Nephrology and Hypertension, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Departments of Nephrology and Hypertension, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Departments of Nephrology and Hypertension, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Departments of Nephrology and Hypertension, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Departments of Nephrology and Hypertension, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Department of Medical Science, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Departments of Nephrology and Hypertension, Kawasaki Medical School | ||||||
著者所属(英) | ||||||
en | ||||||
Departments of Nephrology and Hypertension, Kawasaki Medical School | ||||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Diabetic kidney disease | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Glucagon-like peptide-1 | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Endothelial dysfunction | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Oxidative stress | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Glomerular permeability | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Glycocalyx | |||||
抄録(英) | ||||||
en | ||||||
Background: In most developed countries, diabetic kidney disease is the most common cause of chronic kidney disease, leading to end-stage renal disease, and it is also associated with cardiovascular diseases, including heart failure, and a higher risk of other microvascular complications. A recent clinical trial indicated that the dipeptidyl peptidase-4 inhibitor linagliptin prevents the occurrence and progression of albuminuria in patients with type 2 diabetes. Thus, this study aimed to elucidate the molecular mechanism underlying the inhibitory effect of linagliptin on albuminuria in diabetic kidney disease. Methods: Control C57BL/6 mice and diabetic Ins2+/Akita mice were orally administered linagliptin (5 mg/kg/ day) every day for 8 weeks. Results: Compared to control mice, Ins2+/Akita mice had markedly elevated blood glucose and HbA1c levels, but there were no significant changes after linagliptin treatment. Furthermore, albuminuria and urinary 8-OHdG levels were significantly increased and glomerular mesangial area was significantly expanded in Ins2+/Akita mice compared to those in control mice; these changes were ameliorated by linagliptin treatment, which also improved the degradation of glomerular endothelial glycocalyx and enhancement of glomerular permeability of macromolecules. The activity of AMP-activated protein kinase and the expression of guanosine 5'-triphosphate cyclohydrolase I in human glomerular endothelial cells were significantly lower in high glucose conditions and were improved by linagliptin or GLP-1 administration. Discussion: These results together suggest that linagliptin reduced albuminuria in a blood glucose-independent manner via the reduction of oxidative stress and maintenance of the glycocalyx in endothelial cells. Thus, earlier treatment with linagliptin may slow the progression of diabetic kidney disease. | ||||||
書誌情報 |
en : Kawasaki medical journal 巻 47, p. 131-141, 発行日 2021 |
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出版者 | ||||||
出版者 | Kawasaki Medical Society | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 03850234 | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 24343404 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA12685295 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA12029005 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.11482/KMJ-E202147131 | |||||
記事種別(英) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Regular Article | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://igakkai.kms-igakkai.com/wp/wp-content/uploads/2021en/KMJ-E202147131.pdf | |||||
関連名称 | https://igakkai.kms-igakkai.com/wp/wp-content/uploads/2021en/KMJ-E202147131.pdf | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 |