Glucolipotoxicity in Pancreatic β-Cells.
Glucolipotoxicity in Pancreatic β-Cells.
复制标题
DOI：
10.4093/dmj.2011.35.5.444
复制
发表时间：
2011-10
影响因子：
5.9
通讯作者：
Yoon KH
中科院分区：
文献类型：
--
作者：
Kim JW;Yoon KH
亚洲最近的2型糖尿病流行在几个关键领域与世界其他地区报道的不同：它的演变时间要短得多，在生命的早期阶段，而且在体重指数较低的人群中。患者的这些表型特征强烈表明，胰岛素分泌缺陷可能在糖尿病的发生和发展中发挥更重要的作用。遗传因素显然是β细胞功能障碍和β细胞质量不足的基础；然而，一些可改变的因素也与β细胞恶化有关，最明显的是慢性高血糖和游离脂肪酸水平升高。无论是葡萄糖还是游离脂肪酸本身都不会引起临床上有意义的β细胞毒性，尤其是在糖耐量正常或受损的患者中。因此，用“糖脂毒性”一词来描述这一现象可能更合适。目前已经提出了多种机制来解释糖中毒导致的β细胞功能障碍和死亡，但其主要因素似乎是通过改变细胞内能量代谢和氧化应激抑制关键转录因子基因的表达。因此，稳定糖脂毒性引起的β-细胞代谢变化是治疗2型糖尿病的新途径。
The recent epidemic of type 2 diabetes in Asia differs from that reported in other regions of the world in several key areas: it has evolved over a much shorter time, in an earlier stage of life, and in people with lower body mass indices. These phenotypic characteristics of patients strongly suggest that insulin secretory defects may perform a more important function in the development and progression of diabetes. A genetic element clearly underlies β-cell dysfunction and insufficient β-cell mass; however, a number of modifiable factors are also linked to β-cell deterioration, most notably chronic hyperglycemia and elevated free fatty acid (FFA) levels. Neither glucose nor FFAs alone cause clinically meaningful β-cell toxicity, especially in patients with normal or impaired glucose tolerance. Thus the term "glucolipotoxicity" is perhaps more appropriate in describing the phenomenon. Several mechanisms have been proposed to explain glucolipotoxicity-induced β-cell dysfunction and death, but its major factors appear to be depression of key transcription factor gene expression by altered intracellular energy metabolism and oxidative stress. Therefore, stabilization of metabolic changes induced by glucolipotoxicity in β-cells represents a new avenue for the treatment of type 2 diabetes mellitus.