Calpains and their multiple roles in diabetes mellitus
Calpains and their multiple roles in diabetes mellitus
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DOI：
10.1196/annals.1372.011
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Phoenix, David A.
中科院分区：
文献类型：
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作者：
Harris, Frederick;Biswas, Suman;Phoenix, David A.
2型糖尿病(T2 DM)可在不治疗的情况下导致死亡，据预测，到2010年，这一疾病将影响全球2.15亿人。T2 DM是一种多因素疾病，其确切的遗传原因和生化缺陷尚未完全阐明，但在这两个水平上，钙调蛋白似乎都起到了作用。定位克隆研究定位了编码细胞内半胱氨酸蛋白酶CAPN10的基因CAPN10对T2 DM的易感性。进一步的研究表明，CAPN10中的一些非编码多态与T2 DM功能相关，而编码多态的鉴定表明，突变的Calain 10蛋白也可能与T2 DM有关。在这里，我们回顾了最近的研究，除了后一种酶，还将Calain 5、Calain 3及其剪接变异体、calain 2和calain 1与T2 DM相关的代谢途径以及T2 DM相关表型(如肥胖和胰岛素分泌障碍)以及T2 DM相关并发症(如上皮功能障碍和糖尿病白内障)联系在一起。
Type 2 diabetes mellitus (T2DM) can lead to death without treatment and it has been predicted that the condition will affect 215 million people worldwide by 2010. T2DM is a multifactorial disorder whose precise genetic causes and biochemical defects have not been fully elucidated, but at both levels, calpains appear to play a role. Positional cloning studies mapped T2DM susceptibility to CAPN10, the gene encoding the intracellular cysteine protease, calpain 10. Further studies have shown a number of noncoding polymorphisms in CAPN10 to be functionally associated with T2DM while the identification of coding polymorphisms, suggested that mutant calpain 10 proteins may also contribute to the disease. Here we review recent studies, which in addition to the latter enzyme, have linked calpain 5, calpain 3, and its splice variants, calpain 2 and calpain 1 to T2DM-related metabolic pathways along with T2DM-associated phenotypes, such as obesity and impaired insulin secretion, and T2DM-related complications, such as epithelial dysfunction and diabetic cataract.