Khadija Syeda G, Chen Fei, Hadden Timothy, Commissaris Randall L, Kowluru Anjaneyulu
B4237, Research Service, John D. Dingell VA Medical Center, 4646 John R, Detroit, MI 48201; USA.
Recent Pat Endocr Metab Immune Drug Discov. 2015;9(2):111-20. doi: 10.2174/1872214809666151009120402.
Nuclear lamins, namely lamins A, B and C, surround the nucleoplasmic contents in a meshlike network called the nuclear lamina. These intermediate filaments provide a structural framework to the nuclear envelope (NE), play a role in arrangement of the chromatin within the nucleus, in DNA replication and also participate in DNA damage repair. In order for lamins to be involved in these important nuclear processes and to be functionally active, they undergo a series of post-translational modifications (farnesylation, endoproteolytic cleavage, carboxylmethylation etc.), of which farnesylation is the most studied. Improper farnesylation of lamin proteins, especially lamin A, leads to a number of diseases affecting the striated muscle (e.g. Emery- Dreifuss Muscular Dystrophy, Dilated Cardiomyopathy), adipose tissue (e.g. Dunnigan-type familial partial lipodystrophy) and could result in abnormal senescence and growth deformities (e.g. Progeria syndrome); these are referred to as laminopathies. Despite the existing literature and evidence regarding functions of lamins and diseases associated with abnormal lamin processing, a lot remains to be understood in regards to lamin biology and their role as potential therapeutic targets. In this brief review, we have attempted to summarize the roles of lamins in physiology and pathology of the cell and in type 2 diabetes mellitus [T2DM] and also enlisted patents on methods, systems and devices developed for improving pancreatic beta cell function in diabetes mellitus.
核纤层蛋白，即核纤层蛋白A、B和C，以一种称为核纤层的网状结构围绕着核质内容物。这些中间丝为核膜（NE）提供了一个结构框架，在细胞核内染色质的排列、DNA复制中发挥作用，还参与DNA损伤修复。为了使核纤层蛋白参与这些重要的核过程并具有功能活性，它们会经历一系列翻译后修饰（法尼基化、内切蛋白水解切割、羧甲基化等），其中法尼基化是研究最多的。核纤层蛋白，尤其是核纤层蛋白A的法尼基化不当会导致多种影响横纹肌的疾病（如埃默里 - 德赖富斯肌营养不良症、扩张型心肌病）、脂肪组织疾病（如邓尼根型家族性部分脂肪营养不良症），并可能导致异常衰老和生长畸形（如早衰综合征）；这些被称为核纤层蛋白病。尽管已有关于核纤层蛋白功能以及与异常核纤层蛋白加工相关疾病的文献和证据，但关于核纤层蛋白生物学及其作为潜在治疗靶点的作用仍有许多有待了解之处。在这篇简短的综述中，我们试图总结核纤层蛋白在细胞生理和病理以及2型糖尿病（T2DM）中的作用，并列举了为改善糖尿病患者胰腺β细胞功能而开发的方法、系统和装置的专利。
