| 論文名 |
Cyclodextrin protects podocytes in diabetic kidney disease. |
| 著者 |
Sandra Merscher-Gomez
Johanna Guzman
Christopher E Pedigo
Markku Lehto
Robier Aguillon-Prada
Armando Mendez
Mariann I Lassenius
Carol Forsblom
Taehyun Yoo
Rodrigo Villarreal
Dony Maiguel
Kevin Johnson
Ronald Goldberg
Viji Nair
Ann Randolph
Matthias Kretzler
Robert G Nelson
George W Burke 3rd
Per-Henrik Groop
Alessia Fornoni
FinnDiane Study Group
|
| キーワード |
|
| 出版年月 |
1970年1月 |
| 発表先 |
Diabetes. 2013 Nov;62(11):3817-27. |
| WEBサイト |
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| 論文概要（和文） |
シクロデキストリンは糖尿病性腎疾患の足細胞を保護します。 |
| 論文概要（英文） |
Diabetic kidney disease (DKD) remains the most common cause of end-stage kidney disease despite multifactorial intervention. We demonstrated that increased cholesterol in association with downregulation of ATP-binding cassette transporter ABCA1 occurs in normal human podocytes exposed to the sera of patients with type 1 diabetes and albuminuria (DKD(+)) when compared with diabetic patients with normoalbuminuria (DKD(-)) and similar duration of diabetes and lipid profile. Glomerular downregulation of ABCA1 was confirmed in biopsies from patients with early DKD (n = 70) when compared with normal living donors (n = 32). Induction of cholesterol efflux with cyclodextrin (CD) but not inhibition of cholesterol synthesis with simvastatin prevented podocyte injury observed in vitro after exposure to patient sera. Subcutaneous administration of CD to diabetic BTBR (black and tan, brachiuric) ob/ob mice was safe and reduced albuminuria, mesangial expansion, kidney weight, and cortical cholesterol content. This was followed by an improvement of fasting insulin, blood glucose, body weight, and glucose tolerance in vivo and improved glucose-stimulated insulin release in human islets in vitro. Our data suggest that impaired reverse cholesterol transport characterizes clinical and experimental DKD and negatively influences podocyte function. Treatment with CD is safe and effective in preserving podocyte function in vitro and in vivo and may improve the metabolic control of diabetes. |
