β-cell adaptation and decompensation during the progression of diabetes
β-cell adaptation and decompensation during the progression of diabetes
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DOI：
10.2337/diabetes.50.2007.s154
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发表时间：
2001-02-01
期刊：
影响因子：
7.7
通讯作者：
Sharma, A
中科院分区：
文献类型：
--
作者：
Weir, GC;Laybutt, DR;Sharma, A
β细胞功能不足是所有糖尿病的重要组成部分。最明显的问题是无法维持足够的β细胞数量和功能来科普任何存在的胰岛素抵抗。最显著的功能缺陷是急性葡萄糖诱导的胰岛素分泌（GIIS）的丧失。这篇综述讨论了β细胞成功地适应增加的需求，然后随着糖尿病的发展而失代偿的方式。成功的适应是通过增加β细胞质量和增加胰岛素分泌来实现的。探讨了暴露于糖尿病环境的β细胞失去分化，从而导致GIIS等专门功能的丧失的假设。通过在部分胰腺切除术的大鼠模型中发现β-细胞的去分化（包括胰岛素基因表达的减少），这可能进一步导致胰岛素产生的减少，加强了这一概念。另一个发现是c-Myc的表达增加，这可能有助于乳酸脱氢酶表达的增加和β细胞肥大的发展。有观点认为，糖尿病中发现的β细胞变化与葡萄糖水平升高的相关性优于与非酯化脂肪酸水平的相关性，因此支持葡萄糖毒性的重要性。
Inadequate beta -cell function is an essential component of all forms of diabetes. The most obvious problem is a failure to maintain sufficient beta -cell mass and function to cope with whatever insulin resistance is present. The most striking functional defect is a loss of acute glucose-induced insulin secretion (GIIS). This review discusses the ways in which beta -cells successfully adapt to increased demand and then decompensate as diabetes develops. Successful adaptation is achieved through increased beta -cell mass and increased insulin secretion. The hypothesis is explored that beta -cells exposed to the diabetic milieu lose their differentiation, which leads to loss of specialized functions such as GIIS. This concept has been strengthened by the finding of dedifferentiation of beta -cells in a rat model of partial pancreatectomy that includes a reduction of insulin gene expression, which may further contribute to decreased insulin production. Another finding was increased expression of c-Myc, which probably contributes to an increase in the expression of lactate dehydrogenase and the development of beta -cell hypertrophy. Arguments are developed that the beta -cell changes found in diabetes are better correlated with increased glucose levels than with nonesterified fatty acid levels, thus supporting the importance of glucose toxicity.