کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2797994 1155673 2008 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Protein kinase C-β inhibition for diabetic kidney disease
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی علوم غدد
پیش نمایش صفحه اول مقاله
Protein kinase C-β inhibition for diabetic kidney disease
چکیده انگلیسی

Amid the rapidly rising number of people with diabetes worldwide, the prevalence of diabetic kidney disease (DKD) is expected to increase considerably despite available treatments. Consequently, novel therapeutic agents are urgently needed. Ruboxistaurin mesylate is a bisindolylmaleimide that specifically inhibits the β isoform of protein kinase C (PKC). In experimental models of DKD, ruboxistaurin normalized glomerular hyperfiltration, decreased urinary albumin excretion, preserved kidney function, and reduced mesangial expansion, glomerulosclerosis, and tubulointerstitial fibrosis. These beneficial effects of ruboxistaurin, both alone and combined with renin–angiotensin system inhibition, have been observed in a variety of experimental models of DKD. A phase 2 study of PKC-β inhibition in persons with type 2 diabetes and DKD already treated with angiotensin converting enzyme inhibition and/or angiotensin receptor blockade has been conducted. Addition of ruboxistaurin for 1 year reduced urinary albumin, prevented an increase in urinary transforming growth factor-β, and stabilized estimated glomerular filtration rate. Based on secondary analyses of clinical trials in patients with diabetic retinopathy or neuropathy, ruboxistaurin appears safe and may also prevent onset of DKD. PKC-β inhibition holds promise as a new strategy to improve kidney disease outcomes in diabetes. Large-scale clinical trials will be required to confirm safety and to validate prospective benefits of ruboxistaurin on relevant clinical endpoints in DKD.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Diabetes Research and Clinical Practice - Volume 82, Supplement 1, 13 November 2008, Pages S70–S74
نویسندگان
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