The hexosamine signaling pathway: a new road to drug discovery

The hexosamine signaling pathway: a new road to drug discovery
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己糖胺信号通路:药物发现的新途径

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发表时间:
2002
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影响因子:
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通讯作者:
S. Marshall
S. Marshall
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作者:
S. Marshall

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高血糖是一种病理生理状态,可通过加重潜在的胰岛素抵抗和损害胰岛素分泌来维持和维持2型糖尿病患者的高血糖水平。长期的高血糖会导致视网膜病变、肾病、神经病变和其他血管疾病。现已知,氨基己糖信号通路可以检测高血糖状态,并介导胰岛素抵抗的诱导和基因表达的调节。然而,这一新的葡萄糖传感途径背后的机制(S)还需要阐明。普遍的假说是,氨基己糖信号的细胞作用与胞液和核蛋白的O-连接糖基化密切相关。在这篇综述中,作者讨论了该领域的最新进展,并强调了当前一些氨基己糖研究设计和解释中的潜在陷阱。作者还提出了术语方面的建议,为今后的研究提供了便利。了解高血糖诱导的胰岛素抵抗和葡萄糖介导的糖尿病并发症进展的细胞机制将有助于发现治疗糖尿病的新药。
Hyperglycemia is a pathophysiologic state that can perpetuate and sustain the elevated blood glucose levels in type 2 diabetes mellitus by worsening the underlying insulin resistance and impairing insulin secretion. Prolonged hyperglycemia leads to retinopathy, nephropathy, neuropathy, and other vascular disorders. The hexosamine signaling pathway is now known to detect hyperglycemic conditions and mediate induction of insulin resistance and regulation of gene expression. However, the mechanism(s) underlying this novel glucose-sensing pathway require elucidation. The prevailing hypothesis is that the cellular actions of hexosamine signaling are closely linked to O-linked glycosylation of cytosolic and nuclear proteins. In this review, the author discusses recent advances in the field and highlights potential pitfalls in the design and interpretation of some current hexosamine studies. The author also offers suggestions on terminology to facilitate future studies. Understanding the cellular mechanisms underlying hyperglycemia-induced insulin resistance and the progressive development of glucose-mediated diabetic complications will facilitate the discovery of novel drugs to treat diabetes.
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