Mandrup-Poulsen T
Steno Diabetes Center, Gentofte, Denmark.
Diabetes. 2001 Feb;50 Suppl 1:S58-63. doi: 10.2337/diabetes.50.2007.s58.
Pancreatic beta-cells are sensitive to a number of proapoptotic stimuli. Thus, apoptosis is an important part of the physiological neonatal remodeling of the endocrine pancreas, and a number of pathological stimuli involved in type 1 and type 2 diabetes have been shown to elicit beta-cell apoptosis. Factors of relevance to type 1 diabetes include proinflammatory cytokines, nitric oxide, and reactive oxygen species as well as Fas ligand. Recent findings that free fatty acids, glucose, sulfonylurea, and amylin cause beta-cell apoptosis in vitro suggest that programmed cell death may also be involved in the pathogenesis of type 2 diabetes. Furthermore, there is evidence favoring a convergence in signaling pathways toward common effectors of beta-cell apoptosis elicited by stimuli implicated in the pathogenesis of type 1 and type 2 diabetes. Therefore, recent studies involving the stimuli and signaling pathways of beta-cell apoptosis-in particular, mitogen- and stress-activated protein kinases-will be reviewed. It is concluded that immunological, inflammatory, and metabolic signals cause beta-cell apoptosis, and the possibility that these signals converge toward a common beta-cell death signaling pathway should be investigated further.
胰腺β细胞对多种促凋亡刺激敏感。因此，细胞凋亡是内分泌胰腺生理性新生儿重塑的重要组成部分，并且已表明参与1型和2型糖尿病的许多病理刺激会引发β细胞凋亡。与1型糖尿病相关的因素包括促炎细胞因子、一氧化氮、活性氧以及Fas配体。最近的研究发现，游离脂肪酸、葡萄糖、磺脲类药物和胰淀素在体外可导致β细胞凋亡，这表明程序性细胞死亡可能也参与了2型糖尿病的发病机制。此外，有证据支持在1型和2型糖尿病发病机制中涉及的刺激所引发的β细胞凋亡的共同效应器的信号通路存在趋同现象。因此，将对近期涉及β细胞凋亡的刺激和信号通路——特别是丝裂原和应激激活蛋白激酶——的研究进行综述。得出的结论是，免疫、炎症和代谢信号会导致β细胞凋亡，并且这些信号趋向于共同的β细胞死亡信号通路的可能性应进一步研究。
