β-cells in type 2 diabetes:: A loss of function and mass
β-cells in type 2 diabetes:: A loss of function and mass
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DOI：
10.1159/000080503
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Donath, MY
中科院分区：
文献类型：
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作者：
Maedler, K;Donath, MY
2型糖尿病表现为在面对胰岛素抵抗时失去产生足够量的胰岛素以维持正常血糖的能力的个体。分泌足量胰岛素的能力取决于β细胞的功能和质量。慢性高脂血症对胰腺β细胞有害，导致胰岛素分泌受损，并在β细胞更新的调节中发挥重要作用。本文将讨论长期升高的葡萄糖水平对β细胞周转和功能的影响。在以前的研究中，我们已经表明，由于组成型表达的Fas配体和上调的Fas之间的相互作用，升高的葡萄糖浓度诱导人β细胞凋亡。人类β细胞产生白细胞介素（IL）-1 β，以响应高浓度的葡萄糖，独立于免疫介导的过程。这被IL-1受体拮抗剂（IL-1 Ra）拮抗，IL-1 Ra是一种也存在于β细胞中的天然抗炎细胞因子。因此，IL-1 β和IL-1 Ra的平衡可能在糖尿病的发病机制中起着至关重要的作用。抑制葡萄糖毒性代表了糖尿病治疗中保留功能性β细胞群的有前景的治疗策略。版权所有（C）2004 S. Karger AG，巴塞尔。
Type 2 diabetes mellitus manifests itself in individuals who lose the ability to produce sufficient amounts of insulin to maintain normoglycaemia in the face of insulin resistance. The ability to secrete adequate amounts of insulin depends on beta-cell function and mass. Chronic hyperglycaemia is detrimental to pancreatic beta-cells, causing impaired insulin secretion and playing an essential role in the regulation of beta-cell turnover. This paper will address the effect of chronically elevated glucose levels on beta-cell turnover and function. In previous studies we have shown that elevated glucose concentrations induce apoptosis in human beta-cells due to an interaction between constitutively expressed Fas ligand and upregulated Fas. Human beta-cells produce interleukin (IL)-1beta in response to high glucose concentrations, independently of an immune-mediated process. This was antagonized by the IL-1 receptor antagonist (IL-1Ra), a naturally occurring anti-inflammatory cytokine also found in the beta-cell. Therefore the balance of IL-1beta and IL-1Ra may play a crucial role in the pathogenesis of diabetes. Inhibition of glucotoxicity represents a promising therapeutic stratagem in diabetes therapy to preserve functional beta-cell mass. Copyright (C) 2004 S. Karger AG, Basel.