Type 2 diabetes - unmet need, unresolved pathogenesis, mTORC1-centric paradigm.
Type 2 diabetes - unmet need, unresolved pathogenesis, mTORC1-centric paradigm.
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2型糖尿病 - 未满足的需求，未解决的发病机理，以MTORC1为中心的范例。
DOI：
10.1007/s11154-020-09545-w
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发表时间：
2020-12
影响因子：
8.2
通讯作者：
Bar-Tana J
中科院分区：
文献类型：
--
作者：
Bar-Tana J
2型糖尿病（T2 D）的当前范例是以葡萄糖为中心的，仅按血糖特征分类。以葡萄糖为中心的范式将高血糖症视为主要目标，由胰岛素抵抗和进行性β细胞衰竭驱动，并将血糖控制视为最终治疗目标。最重要的是，以葡萄糖为中心的范式考虑了与T2 D相关的非血糖性疾病，例如，肥胖、血脂异常、高血压、大血管疾病、微血管疾病和脂肪肝作为“风险因素”和/或“结局”和/或“合并症”，而不是T2 D的原发性固有疾病方面。尽管其患病率很高（60-90%），并且在分析T2 D发病率和死亡率方面发挥着重要作用。此外，以葡萄糖为中心的范式未能认识到T2 D的非血糖疾病是由胰岛素驱动的，并且除了血糖控制之外，T2 D中对胰岛素的反应基本上是规则而不是例外。以葡萄糖为中心的范式未能提供T2 D的血糖和非血糖疾病的详尽统一观点，可能导致T2 D仍然是一个未满足的需求。以mTORC 1为中心的范式认为，过度活跃的mTORC 1驱动T2 D的血糖和非血糖疾病方面。高活性mTORC 1被认为是一种双刃剑，即通过破坏胰岛素受体-Akt转导通路来干扰血糖控制，同时伴随着T2 D的非血糖疾病。以mTORC 1为中心的范式可能为T2 D的发病机制、临床焦点和治疗策略提供新的视角。
The current paradigm of type 2 diabetes (T2D) is gluco-centric, being exclusively categorized by glycemic characteristics. The gluco-centric paradigm views hyperglycemia as the primary target, being driven by resistance to insulin combined with progressive beta cells failure, and considers glycemic control its ultimate treatment goal. Most importantly, the gluco-centric paradigm considers the non-glycemic diseases associated with T2D, e.g., obesity, dyslipidemia, hypertension, macrovascular disease, microvascular disease and fatty liver as ‘risk factors’ and/or ‘outcomes’ and/or ‘comorbidities’, rather than primary inherent disease aspects of T2D. That is in spite of their high prevalence (60–90%) and major role in profiling T2D morbidity and mortality. Moreover, the gluco-centric paradigm fails to realize that the non-glycemic diseases of T2D are driven by insulin and, except for glycemic control, response to insulin in T2D is essentially the rule rather than the exception. Failure of the gluco-centric paradigm to offer an exhaustive unifying view of the glycemic and non-glycemic diseases of T2D may have contributed to T2D being still an unmet need. An mTORC1-centric paradigm maintains that hyperactive mTORC1 drives the glycemic and non-glycemic disease aspects of T2D. Hyperactive mTORC1 is proposed to act as double-edged agent, namely, to interfere with glycemic control by disrupting the insulin receptor-Akt transduction pathway, while concomitantly driving the non-glycemic diseases of T2D. The mTORC1-centric paradigm may offer a novel perspective for T2D in terms of pathogenesis, clinical focus and treatment strategy.
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影响因子：
15.9
作者：
Cusi, K;Maezono, K;Mandarino, LJ
通讯作者：
Mandarino, LJ
影响因子：
4.1
作者：
Chen, Weiyi;Balland, Eglantine;Cowley, Michael A.
通讯作者：
Cowley, Michael A.
影响因子：
37.8
作者：
Barr, Elizabeth L. M.;Zimmet, Paul Z.;Shaw, Jonathan E.
通讯作者：
Shaw, Jonathan E.
影响因子：
16.2
作者：
Bommer, Christian;Sagalova, Vera;Vollmer, Sebastian
通讯作者：
Vollmer, Sebastian
影响因子：
7.7
作者：
Butler, AE;Janson, J;Butler, PC
通讯作者：
Butler, PC