Diabetic Nephropathy: Perspective on Novel Molecular Mechanisms

被引:263
作者
Gnudi, Luigi [1 ]
Coward, Richard J. M. [2 ]
Long, David A. [3 ]
机构
[1] Kings Coll London, Cardiovasc Div, London SE1 9NH, England
[2] Univ Bristol, Acad Renal Unit, Dorothy Hodgkin Bldg,Whitson St, Bristol BS1 3NY, Avon, England
[3] UCL, Inst Child Hlth, Dev Biol & Canc Programme, London WC1N 1EH, England
基金
英国惠康基金; 英国医学研究理事会;
关键词
ENDOPLASMIC-RETICULUM STRESS; INSULIN-RESISTANCE; KIDNEY-DISEASE; BLOOD-PRESSURE; OXIDATIVE STRESS; HIGH GLUCOSE; URSODEOXYCHOLIC ACID; GLOMERULAR PODOCYTE; EMERGING ROLE; SODIUM-INTAKE;
D O I
10.1016/j.tem.2016.07.002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Diabetes mellitus (DM) is the major cause of end-stage renal disease (ESRD) globally, and novel treatments are urgently needed. Current therapeutic approaches for diabetic nephropathy (DN) are focussing on blood pressure control with inhibitors of the renin-angiotensin-aldosterone system, on glycaemic and lipid control, and life-style changes. In this review, we highlight new molecular insights aiding our understanding of the initiation and progression of DN, including glomerular insulin resistance, dysregulation of cellular substrate utilisation, podocyte-endothelial communication, and inhibition of tubular sodium coupled glucose reabsorption. We believe that these mechanisms offer new therapeutic targets that can be exploited to develop important renoprotective treatments for DN over the next decade.
引用
收藏
页码:820 / 830
页数:11
相关论文
共 89 条
[1]   Renoprotective Effects of Fenofibrate via Modulation of LKB1/AMPK mRNA Expression and Endothelial Dysfunction in a Rat Model of Diabetic Nephropathy [J].
Al-Rasheed, Nawal M. ;
Al-Rasheed, Nouf M. ;
Attia, Hala A. ;
Al-Amin, Maha A. ;
Al-Ajmi, Hanaa N. ;
Hasan, Iman H. ;
Mohamad, Raeesa A. ;
Sinjilawi, Nasr A. .
PHARMACOLOGY, 2015, 95 (5-6) :229-239
[2]   Signaling at the slit diaphragm [J].
Benzing, T .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2004, 15 (06) :1382-1391
[3]   Biochemistry and molecular cell biology of diabetic complications [J].
Brownlee, M .
NATURE, 2001, 414 (6865) :813-820
[4]   ACE2, a new regulator of the renin-angiotensin system [J].
Burrell, LM ;
Johnston, CI ;
Tikellis, C ;
Cooper, ME .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2004, 15 (04) :166-169
[5]   INSULIN-RECEPTORS ALONG THE RAT NEPHRON - [I125] INSULIN BINDING IN MICRODISSECTED GLOMERULI AND TUBULES [J].
BUTLEN, D ;
VADROT, S ;
ROSEAU, S ;
MOREL, F .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1988, 412 (06) :604-612
[6]   AKT2 is essential to maintain podocyte viability and function during chronic kidney disease [J].
Canaud, Guillaume ;
Bienaime, Frank ;
Viau, Amandine ;
Treins, Caroline ;
Baron, William ;
Nguyen, Clement ;
Burtin, Martine ;
Berissi, Sophie ;
Giannakakis, Konstantinos ;
Muda, Andrea Onetti ;
Zschiedrich, Stefan ;
Huber, Tobias B. ;
Friedlander, Gerard ;
Legendre, Christophe ;
Pontoglio, Marco ;
Pende, Mario ;
Terzi, Fabiola .
NATURE MEDICINE, 2013, 19 (10) :1288-+
[7]   Ursodeoxycholic acid and 4-phenylbutyrate prevent endoplasmic reticulum stress-induced podocyte apoptosis in diabetic nephropathy [J].
Cao, Ai-Li ;
Wang, Li ;
Chen, Xia ;
Wang, Yun-Man ;
Guo, Heng-Jiang ;
Chu, Shuang ;
Liu, Cheng ;
Zhang, Xue-Mei ;
Peng, Wen .
LABORATORY INVESTIGATION, 2016, 96 (06) :610-622
[8]   Role of endoplasmic reticulum stress in apoptosis of differentiated mouse podocytes induced by high glucose [J].
Cao, Yanping ;
Hao, Yongmei ;
Li, Hang ;
Liu, Qingjuan ;
Gao, Feng ;
Liu, Wei ;
Duan, Huijun .
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2014, 33 (04) :809-816
[9]   Renal Protective Effects of Toll-like Receptor 4 Signaling Blockade in Type 2 Diabetic Mice [J].
Cha, J. J. ;
Hyun, Y. Y. ;
Lee, M. H. ;
Kim, J. E. ;
Nam, D. H. ;
Song, H. K. ;
Kang, Y. S. ;
Lee, J. E. ;
Kim, H. W. ;
Han, J. Y. ;
Cha, D. R. .
ENDOCRINOLOGY, 2013, 154 (06) :2144-2155
[10]   The Bioenergetic Health Index is a sensitive measure of oxidative stress in human monocytes [J].
Chacko, Balu K. ;
Zhi, Degui ;
Darley-Usmar, Victor M. ;
Mitchell, Tanecia .
REDOX BIOLOGY, 2016, 8 :43-50