Important role of heparan sulfate in postnatal islet growth and insulin secretion
Important role of heparan sulfate in postnatal islet growth and insulin secretion
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DOI：
10.1016/j.bbrc.2009.03.140
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发表时间：
2009-05-22
影响因子：
3.1
通讯作者：
Sugawara, Akira
中科院分区：
文献类型：
--
作者：
Takahashi, Iwao;Noguchi, Naoya;Sugawara, Akira
硫酸乙酰肝素 (HS) 与多种信号分子结合并调节配体-受体相互作用，在胚胎发育中发挥重要作用。在这里，我们发现 HS 在小鼠 1 周龄后在胰岛 β 细胞中密集表达。酶促去除分离胰岛中的 HS 导致葡萄糖诱导的胰岛素分泌减弱，同时胰岛素分泌机制中几个关键组件的基因表达减少。我们通过使 β 细胞中的外骨蛋白肿瘤样 3 基因失活来进一步耗尽胰岛 HS。这些休战表现出异常的胰岛形态，1周龄后β细胞增殖减少，并且由于胰岛素分泌缺陷而出现葡萄糖不耐症。这些结果表明，胰岛 HS 参与出生后胰岛成熟的调节，并且是确保正常胰岛素分泌所必需的。 (C) 2009 Elsevier Inc. 保留所有权利。
Heparan sulfate (HS) binds with several signaling molecules and regulates ligand-receptor interactions, playing an essential role in embryonic development. Here we showed that HS was intensively expressed in pancreatic islet beta-cells after I week of age in mice. The enzymatic removal of HS in isolated islets resulted in attenuated glucose-induced insulin secretion with a concomitant reduction in gene expression of several key components in the insulin secretion machinery. We further depleted islet HS by inactivating the exostosin tumor-like 3 gene specifically in beta-cells. These truce exhibited abnormal islet morphology with reduced beta-cell proliferation after 1 week of age and glucose intolerance due to defective insulin secretion. These results demonstrate that islet HS is involved in the regulation of postnatal islet maturation and required to ensure normal insulin secretion. (C) 2009 Elsevier Inc. All rights reserved.