Progressive change of intra-islet GLP-1 production during diabetes development.
Progressive change of intra-islet GLP-1 production during diabetes development.
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DOI：
10.1002/dmrr.2534
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发表时间：
2014-11
影响因子：
8
通讯作者：
Wu, Hongju
中科院分区：
文献类型：
--
作者：
O'Malley, Thomas J.;Fava, Genevieve E.;Zhang, Yanqing;Fonseca, Vivian A.;Wu, Hongju
胰高血糖素样肽1(GLP-1)和胰高血糖素具有相同的前体分子原胰高血糖素，但各自以组织特异性的方式来自不同的翻译后过程。最近的研究表明，在胰岛细胞中，GLP-1与胰高血糖素共表达。本研究旨在探讨GLP-1与胰岛高血糖素在糖尿病发生发展过程中的渐进性变化。本研究采用1型(NOD小鼠)和2型(db/db小鼠)糖尿病模型。这些小鼠被密切监测其糖尿病进展情况，并根据它们的血糖水平在不同的阶段被处死。免疫组织化学方法检测大鼠胰岛GLP-1和胰高血糖素的表达。定量分析以评估这些变化的意义。在db/db小鼠中，随着糖尿病的发展，胰岛中表达GLP-1的细胞与表达胰高血糖素的细胞的比率呈显著的进行性增加。GLP-1表达增加与PC1/3表达上调相一致。有趣的是，在NOD小鼠的1型糖尿病发展过程中，胰岛内GLP-1的表达没有明显变化。这项研究表明，在2型糖尿病的发展过程中，GLP-1在胰岛中的表达逐渐上调。此外，数据还表明，1型和2型糖尿病患者胰岛内GLP-1的产生存在明显差异。这些差异可能会对这些疾病的临床和病理生理过程产生影响，并可能成为治疗方法的目标。
Glucagon-like Peptide 1 (GLP-1) and glucagon shares the same precursor molecule proglucagon, but each arises from a distinct posttranslational process in a tissue-specific manner. Recently it has been shown that GLP-1 is co-expressed with glucagon in pancreatic islet cells. This study was aimed to investigate the progressive changes of GLP-1 vs glucagon production in pancreatic islets during the course of diabetes development. Both type 1 (NOD mice) and type 2 (db/db mice) diabetes models were employed in this study. The mice were monitored closely for their diabetes progression, and were sacrificed at different stages according to their blood glucose levels. GLP-1 and glucagon expression in the pancreatic islets was examined using immunohistochemistry assays. Quantitative analysis was performed to evaluate the significance of the changes. The ratio of GLP-1-expressing cells to glucagon expressing cells in the islets showed significant, progressive increase with the development of diabetes in db/db mice. The increase of GLP-1 expression was in accordance with the upregulation of PC1/3 expression in these cells. Interestingly, intra-islet GLP-1 expression was not significantly changed during the development of type 1 diabetes in NOD mice. The study demonstrated GLP-1 was progressively up-regulated in pancreatic islets during type 2 diabetes development. In addition, the data suggest clear differences in intra-islet GLP-1 production between type 1 and type 2 diabetes developments. These differences may have an impact on the clinical and pathophysiological processes of these diseases and may be a target for therapeutic approaches.
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影响因子：
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