Diabetes in Friedreich Ataxia

被引:59
作者
Cnop, Miriam [1 ,2 ]
Mulder, Hindrik [3 ]
Igoillo-Esteve, Mariana [1 ]
机构
[1] Univ Libre Bruxelles, Expt Med Lab, B-1070 Brussels, Belgium
[2] Erasmus Hosp, Div Endocrinol, Brussels, Belgium
[3] Lund Univ, Ctr Diabet, Unit Mol Metab, Malmo, Sweden
关键词
apoptosis; diabetes; Friedreich ataxia; insulin; insulin resistance; pancreatic beta cell; BETA-CELL APOPTOSIS; ENDOPLASMIC-RETICULUM STRESS; FRATAXIN DEFICIENCY; MITOCHONDRIAL DYSFUNCTION; INSULIN-RESISTANCE; 1ST-DEGREE RELATIVES; GLUCOSE-INTOLERANCE; NEURONAL TRAITS; MOUSE MODELS; IRON;
D O I
10.1111/jnc.12216
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Diabetes is a common metabolic disorder in patients with Friedreich ataxia. In this Supplement article, we review the clinical data on diabetes in Friedreich ataxia, and the experimental data from rodent and in vitro models of the disease. Increased body adiposity and insulin resistance are frequently present in Friedreich ataxia, but pancreatic cell dysfunction and death are a conditio sine qua non for the loss of glucose tolerance and development of diabetes. The loss of frataxin function in mitochondria accounts for these pathogenic processes in Friedreich ataxia. Mitochondria are essential for the sensing of nutrients by the cell and for the generation of signals that trigger and amplify insulin secretion, known as stimulus-secretion coupling. Moreover, in the intrinsic pathway of apoptosis, pro-apoptotic signals converge on mitochondria, resulting in mitochondrial Bax translocation, membrane permeabilization, cytochrome c release and caspase cleavage. How and at which level frataxin deficiency impacts on these processes in cells is only partially understood. A better understanding of the molecular mechanisms mediating cell demise in Friedreich ataxia will pave the way for new therapeutic approaches.
引用
收藏
页码:94 / 102
页数:9
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