de Koning Eelco J P, Bonner-Weir Susan, Rabelink Ton J
Department of Nephrology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Trends Pharmacol Sci. 2008 Apr;29(4):218-27. doi: 10.1016/j.tips.2008.02.001. Epub 2008 Mar 21.
Type 2 diabetes is characterized by progressive beta-cell dysfunction and a reduction in beta-cell mass. Pancreatic islets are a target for adverse effectors such as high concentrations of glucose, pro-inflammatory cytokines and increased free fatty acid concentrations - which are associated with adiposity, insulin resistance and the induction of beta-cell apoptosis. If the beta-cell mass is already below the threshold for maintaining normoglycemia, the expansion of beta-cell mass is the only option for achieving normoglycemia without the use of additional glucose-lowering agents. Therapies based on glucagon-like peptide-1 and combinations of growth factors such as epidermal growth factor and gastrin are promising new strategies for beta-cell preservation. In this review, we address the mechanisms involved in beta-cell dysfunction and beta-cell loss, and provide a rationale for pharmacological intervention for the preservation and/or expansion of beta-cell mass in type 2 diabetes.
2型糖尿病的特征是β细胞功能进行性障碍和β细胞数量减少。胰岛是诸如高浓度葡萄糖、促炎细胞因子和游离脂肪酸浓度增加等不良效应因子的作用靶点，这些与肥胖、胰岛素抵抗及β细胞凋亡的诱导有关。如果β细胞数量已低于维持正常血糖的阈值，那么在不使用额外降糖药物的情况下，增加β细胞数量是实现正常血糖的唯一选择。基于胰高血糖素样肽-1的疗法以及表皮生长因子和胃泌素等生长因子的联合应用是有望用于保护β细胞的新策略。在本综述中，我们阐述了β细胞功能障碍和β细胞丢失所涉及的机制，并为2型糖尿病中保护和/或增加β细胞数量的药物干预提供了理论依据。
