Insulin resistance (IR) is associated with several metabolic disorders, including type 2 diabetes (T2D). The development of IR in insulin target tissues involves genetic and acquired factors. Persons at genetic risk for T2D tend to develop IR several years before glucose intolerance. Several rodent models for both IR and T2D are being used to study the disease pathogenesis; however, these models cannot recapitulate all the aspects of this complex disorder as seen in each individual. Human pluripotent stem cells (hPSCs) can overcome the hurdles faced with the classical mouse models for studying IR. Human induced pluripotent stem cells (hiPSCs) can be generated from the somatic cells of the patients without the need to destroy a human embryo. Therefore, patient-specific hiPSCs can generate cells genetically identical to IR individuals, which can help in distinguishing between genetic and acquired defects in insulin sensitivity. Combining the technologies of genome editing and hiPSCs may provide important information about the genetic factors underlying the development of different forms of IR. Further studies are required to fill the gaps in understanding the pathogenesis of IR and diabetes. In this review, we summarize the factors involved in the development of IR in the insulin-target tissues leading to diabetes. Also, we highlight the use of hPSCs to understand the mechanisms underlying the development of IR.

中文翻译：

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糖尿病中的胰岛素抵抗：使用诱导性多能干细胞技术的希望。

胰岛素抵抗（IR）与几种代谢异常有关，包括2型糖尿病（T2D）。胰岛素靶组织中IR的发展涉及遗传和后天因素。患有T2D遗传风险的人在糖耐量不全之前数年往往会发展为IR。IR和T2D的几种啮齿动物模型正在用于研究疾病的发病机理。但是，这些模型无法概括每个人所见的复杂性疾病的所有方面。人类多能干细胞（hPSC）可以克服研究IR的经典小鼠模型所面临的障碍。可以从患者的体细胞中产生人类诱导的多能干细胞（hiPSC），而无需破坏人类胚胎。因此，患者特异性hiPSC可以产生与IR个体在基因上相同的细胞，这可以帮助区分胰岛素敏感性的遗传缺陷和获得性缺陷。将基因组编辑技术与hiPSC结合使用可能会提供有关形成不同形式IR的遗传因素的重要信息。需要进一步的研究来填补了解IR和糖尿病发病机理的空白。在这篇综述中，我们总结了导致糖尿病的胰岛素靶组织中IR的发展所涉及的因素。此外，我们重点介绍了使用hPSC来了解IR发展的潜在机制。需要进一步的研究来填补了解IR和糖尿病发病机理的空白。在这篇综述中，我们总结了导致糖尿病的胰岛素靶组织中IR的发展所涉及的因素。此外，我们重点介绍了使用hPSC来了解IR发展的潜在机制。需要进一步的研究来填补了解IR和糖尿病发病机理的空白。在这篇综述中，我们总结了导致糖尿病的胰岛素靶组织中IR的发展所涉及的因素。此外，我们重点介绍了使用hPSC来了解IR发展的潜在机制。