Tamura Yoshiaki, Takubo Kaiyo, Aida Junko, Araki Atsushi, Ito Hideki
Department of Diabetes, Metabolism, and Endocrinology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
Research Team for Geriatric Pathology and Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan.
Geriatr Gerontol Int. 2016 Mar;16 Suppl 1:66-74. doi: 10.1111/ggi.12738.
Type 2 diabetes mellitus (DM) is a disease characterized by dysfunction of various organs. Recent studies have shown a close relationship between DM and telomere attrition in leukocytes. In patients with DM or impaired glucose tolerance, excessive oxidative stress induces damage to telomeres and shortens their length. Furthermore, it is suggested that telomere length is a good surrogate marker for mortality and diabetic complications in DM patients. We recently found that telomere length in pancreatic β-cells is also shortened in DM patients, potentially leading to an impaired capacity for proliferation and insulin secretion, and accelerated cell death. In contrast, leukocyte telomere length has also been reported in patients with obesity or insulin resistance, both of which are frequently associated with type 2 DM. In an animal model, it has been shown that telomere attrition in adipose tissue induces insulin resistance. Taken together, the available data suggest that hyperglycemia, oxidative stress, and telomere attrition in pancreatic β-cells and adipocytes create a vicious cycle that underlies the pathophysiology of type 2 DM. Inhibition of telomere attrition in various organs, including pancreatic β-cells, could be a new approach for preventing the progression of DM and its complications.
2型糖尿病（DM）是一种以多器官功能障碍为特征的疾病。最近的研究表明，DM与白细胞端粒磨损之间存在密切关系。在DM患者或糖耐量受损患者中，过度的氧化应激会导致端粒损伤并缩短其长度。此外，有研究表明，端粒长度是DM患者死亡率和糖尿病并发症的良好替代指标。我们最近发现，DM患者胰腺β细胞中的端粒长度也缩短了，这可能导致其增殖和胰岛素分泌能力受损，并加速细胞死亡。相比之下，肥胖或胰岛素抵抗患者也有白细胞端粒长度的相关报道，这两种情况都经常与2型DM相关。在动物模型中，已经表明脂肪组织中的端粒磨损会诱导胰岛素抵抗。综上所述，现有数据表明，胰腺β细胞和脂肪细胞中的高血糖、氧化应激和端粒磨损形成了一个恶性循环，这是2型DM病理生理学的基础。抑制包括胰腺β细胞在内的各种器官中的端粒磨损，可能是预防DM进展及其并发症的一种新方法。
