Cyclodextrin protects podocytes in diabetic kidney disease.
Cyclodextrin protects podocytes in diabetic kidney disease.
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DOI：
10.2337/db13-0399
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发表时间：
2013-11
期刊：
影响因子：
7.7
通讯作者：
FinnDiane Study Group
中科院分区：
文献类型：
--
作者：
Merscher-Gomez S;Guzman J;Pedigo CE;Lehto M;Aguillon-Prada R;Mendez A;Lassenius MI;Forsblom C;Yoo T;Villarreal R;Maiguel D;Johnson K;Goldberg R;Nair V;Randolph A;Kretzler M;Nelson RG;Burke GW 3rd;Groop PH;Fornoni A;FinnDiane Study Group
尽管进行了多因素干预，糖尿病肾病（DKD）仍然是终末期肾病的最常见原因。我们证明，与白蛋白尿正常 (DKD−) 且糖尿病病程和血脂状况相似的糖尿病患者相比，暴露于 1 型糖尿病伴白蛋白尿 (DKD+) 患者血清的正常人足细胞中，胆固醇升高与 ATP 结合盒转运蛋白 ABCA1 下调相关。与正常活体供体 (n = 32) 相比，早期 DKD 患者 (n = 70) 的活检证实肾小球 ABCA1 下调。用环糊精（CD）诱导胆固醇流出，但用辛伐他汀不抑制胆固醇合成，可以防止暴露于患者血清后在体外观察到的足细胞损伤。对糖尿病 BTBR（黑色和棕褐色，臂尿）ob/ob 小鼠皮下注射 CD 是安全的，并且可以减少蛋白尿、系膜扩张、肾脏重量和皮质胆固醇含量。随后体内空腹胰岛素、血糖、体重和葡萄糖耐量得到改善，体外人胰岛中葡萄糖刺激的胰岛素释放得到改善。我们的数据表明，反向胆固醇转运受损是临床和实验性 DKD 的特征，并对足细胞功能产生负面影响。 CD 治疗在体外和体内保护足细胞功能方面是安全有效的，并且可以改善糖尿病的代谢控制。
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.
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DOI：
10.1083/jcb.200802081
发表时间：
2008-06-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fackler OT;Grosse R
通讯作者：
Grosse R
影响因子：
7.7
作者：
Kruit JK;Wijesekara N;Westwell-Roper C;Vanmierlo T;de Haan W;Bhattacharjee A;Tang R;Wellington CL;LütJohann D;Johnson JD;Brunham LR;Verchere CB;Hayden MR
通讯作者：
Hayden MR
影响因子：
158.5
作者：
Gaede, Peter;Lund-Andersen, Henrik;Pedersen, Oluf
通讯作者：
Pedersen, Oluf
影响因子：
2.9
作者：
Katz, Arie;Udata, Chandrasekhar;Meng, Xu
通讯作者：
Meng, Xu
影响因子：
4.8
作者：
MENDEZ, AJ
通讯作者：
MENDEZ, AJ