Reversible changes in pancreatic islet structure and function produced by elevated blood glucose.
Reversible changes in pancreatic islet structure and function produced by elevated blood glucose.
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DOI：
10.1038/ncomms5639
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发表时间：
2014-08-22
影响因子：
16.6
通讯作者：
Ashcroft, Frances M.
中科院分区：
文献类型：
--
作者：
Brereton, Melissa F.;Iberl, Michaela;Shimomura, Kenju;Zhang, Quan;Adriaenssens, Alice E.;Proks, Peter;Spiliotis, Ioannis I.;Dace, William;Mattis, Katia K.;Ramracheya, Reshma;Gribble, Fiona M.;Reimann, Frank;Clark, Anne;Rorsman, Patrik;Ashcroft, Frances M.
糖尿病的特征是由于胰岛素分泌受损和胰岛细胞功能和/或质量变化导致的胰高血糖素分泌异常而导致的高血糖。高血糖本身在多大程度上导致这些改变仍然知之甚少。在这里，我们发现，成年小鼠中人类激活 KATP 通道突变的 β 细胞特异性表达会导致快速糖尿病以及胰岛形态、超微结构和基因表达的显着改变。慢性高血糖与胰岛中胰岛素阳性细胞的急剧减少和胰高血糖素阳性细胞的增加有关，但细胞更新率没有改变。此外，一些β细胞开始表达胰高血糖素，同时保留许多β细胞特征。这些变化的根源是高血糖，而不是 KATP 通道激活，因为胰岛素治疗可以预防这些变化，而磺脲类药物可以完全逆转这些变化。我们的数据表明，与糖尿病相关的胰岛结构和功能的许多变化可单独归因于高血糖，并且当血糖正常化时，这些变化会逆转。 在糖尿病患者中，由于胰岛结构和功能的改变，胰腺 β 细胞释放的胰岛素减少。在这里，布雷尔顿等人。研究表明，血糖升高是这些变化的基础，并且足以可逆地改变 β 细胞功能障碍小鼠模型中的 β 细胞特性。
Diabetes is characterized by hyperglycaemia due to impaired insulin secretion and aberrant glucagon secretion resulting from changes in pancreatic islet cell function and/or mass. The extent to which hyperglycaemia per se underlies these alterations remains poorly understood. Here we show that β-cell-specific expression of a human activating KATP channel mutation in adult mice leads to rapid diabetes and marked alterations in islet morphology, ultrastructure and gene expression. Chronic hyperglycaemia is associated with a dramatic reduction in insulin-positive cells and an increase in glucagon-positive cells in islets, without alterations in cell turnover. Furthermore, some β-cells begin expressing glucagon, whilst retaining many β-cell characteristics. Hyperglycaemia, rather than KATP channel activation, underlies these changes, as they are prevented by insulin therapy and fully reversed by sulphonylureas. Our data suggest that many changes in islet structure and function associated with diabetes are attributable to hyperglycaemia alone and are reversed when blood glucose is normalized. In patients with diabetes, insulin release from pancreatic β-cells is reduced due to altered islet structure and function. Here, Brereton et al. show that elevated blood glucose underlies these changes and is sufficient to reversibly alter β-cell identity in a mouse model of β-cell dysfunction.
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影响因子：
64.8
作者：
Dor, Y;Brown, J;Melton, DA
通讯作者：
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作者：
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通讯作者：
ASHCROFT, SJH
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158.5
作者：
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通讯作者：
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