Saudek F
Institut klinické a experimentální medicíny, Praha a Centrum bunĕcné terapie a tkánových náhrad Ustav neurovĕd 2. LF UK, Praha.
Cas Lek Cesk. 2003;142(9):523-7.
Multiple genetic factors are involved in the pathogenesis of type 1 and 2 diabetes mellitus. A defect, which could be ascribed to a single or only few genes, has not been established yet. An exception represents the Maturity Onset Diabetes of the Young (MODY) which is rather rare and is caused by mutations in some of 6 known genes. Principles of gene therapy focus mainly on generation of replenishable sources of insulin producing tissue. Which could be used for replacement of the destroyed or failing beta-cells. Current approaches include stimulation of embryonic or adult stem cell proliferation and differentiation into beta-cells, beta-cell proliferation, transdifferentiation of non-islet cells into glucose-sensitive insulin-producing cells and xenotransplantation. Genetic modification is being studied to prevent islet rejection (e.g. local expression of immuno-suppressive cytokines or ligands inducing T-cell apoptosis, knock-out of specific animal genes or transfer of human genes into animal tissue donors) or to construct "superislets" resistant to apoptosis or oxidative stress. For prevention of type 1 diabetes and perhaps for induction of specific immune tolerance vaccination with DNA fragments encoding for specific auto or alloantigens represents a promising approach. In addition, gene therapy offers some hope for the future treatment of diabetic vascular complication, neuropathy and syndromes of insulin resistance.
1型和2型糖尿病的发病机制涉及多种遗传因素。尚未确定可归因于单个或仅少数基因的缺陷。青少年发病的成年型糖尿病（MODY）是个例外，这种病相当罕见，由6种已知基因中的一些基因突变引起。基因治疗的原则主要集中在产生可补充的胰岛素产生组织来源，可用于替代受损或功能衰竭的β细胞。目前的方法包括刺激胚胎干细胞或成体干细胞增殖并分化为β细胞、β细胞增殖、将非胰岛细胞转分化为对葡萄糖敏感的胰岛素产生细胞以及异种移植。正在研究基因修饰以防止胰岛排斥（例如免疫抑制细胞因子或诱导T细胞凋亡的配体的局部表达、敲除特定动物基因或将人类基因转移到动物组织供体中）或构建抗凋亡或抗氧化应激的“超级胰岛”。对于1型糖尿病的预防以及可能诱导特异性免疫耐受，用编码特定自身或同种异体抗原的DNA片段进行疫苗接种是一种有前景的方法。此外，基因治疗为未来治疗糖尿病血管并发症、神经病变和胰岛素抵抗综合征带来了一些希望。
