Molecular mechanisms for insulin resistance in treated HIV-infection.
Molecular mechanisms for insulin resistance in treated HIV-infection.
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DOI：
10.1016/j.beem.2010.10.017
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Hruz PW
中科院分区：
文献类型：
--
作者：
Hruz PW
在寻求提高抗逆转录病毒治疗方案安全性的过程中，鉴定和表征导致接受抗逆转录病毒联合治疗的艾滋病毒感染者胰岛素抵抗高发的分子机制仍然是一个至关重要的目标。体外模型系统的使用以及药物对动物和健康人类志愿者葡萄糖稳态的影响的研究，为了解单个药物对胰岛素抵抗和受影响的细胞途径的贡献提供了重要的见解。HIV蛋白酶抑制剂介导的葡萄糖转运阻断和核苷逆转录酶抑制剂介导的线粒体毒性已经得到了很好的表征。随着对非hiv代谢综合征中胰岛素抵抗介质的理解不断加深，其他细胞效应包括内质网和氧化应激的诱导、脂肪细胞因子分泌的改变和脂肪毒性已被整合到这一发展图景中。这些机制的进一步阐明为持续开发更安全的抗病毒药物和靶向治疗受影响患者的胰岛素抵抗提供了可能。
Identification and characterization of the molecular mechanisms contributing to the high incidence of insulin resistance in HIV infected patients treated with combined antiretroviral therapy remains a critically important goal in the quest to improve the safety of antiretroviral treatment regimens. The use of in vitro model systems together with the investigation of drug-mediated effects on glucose homeostasis in animals and healthy human volunteers has provided important insight into the contribution of individual drugs to insulin resistance and affected cellular pathways. HIV protease inhibitor mediated blockade of glucose transport and nucleoside reverse transcriptase inhibitor mediated mitochondrial toxicity have been well characterized. Together with growing understanding of mediators of insulin resistance in non-HIV metabolic syndrome, additional cellular effects including the induction of endoplasmic reticulum and oxidative stress, altered adipocytokine secretion, and lipotoxicity have been integrated into this developing picture. Further elucidation of these mechanisms provides potential for the continued development of safer antiviral drugs and targeted treatment of insulin resistance in affected patients.
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DOI：
10.1073/pnas.0704212104
发表时间：
2007-08-14
影响因子：
11.1
作者：
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DOI：
10.1152/ajpendo.00167.2007
发表时间：
2008-03-01
影响因子：
5.1
作者：
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