A number of mechanisms have been proposed to explain the well-established link between diabetic status and an increased susceptibility to infection. Notably, diabetes has been shown to be one of the strongest factors influencing healthcare outcome in COVID-19 infections. Though it has long been noted that lymphocytes upregulate insulin receptors following immune activation, until recently, this observation has received little attention. Here, we point out key findings implicating dysregulated insulin signalling in immune cells as a possible contributing factor in the immune pathology associated with diabetes. Mechanistically, insulin, by activating the PI3K/Akt/mTOR pathway, regulates various aspects of both myeloid cells and lymphocytes, such as cell survival, metabolic reprogramming and the polarization and differentiation of immune cells. PI3K signalling is also supressed by immune checkpoint proteins, suggesting that insulin signalling may antagonize peripheral tolerance. Remarkably, it has also recently been shown that, following insulin binding, the insulin receptor translocates to the nucleus where it plays a key role in regulating the transcription of various immune-related genes, including pathways involved in viral infections. Taken together, these observations suggest that dysregulated insulin signalling may directly contribute to a defective immune response during COVID-19 infections.

中文翻译：

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糖尿病和感染易感性：对 COVID-19 的影响

已经提出了许多机制来解释糖尿病状态与感染易感性增加之间的既定联系。值得注意的是，糖尿病已被证明是影响 COVID-19 感染医疗保健结果的最强因素之一。尽管长期以来人们一直注意到淋巴细胞在免疫激活后上调胰岛素受体，但直到最近，这一观察结果才受到关注。在这里，我们指出了一些关键发现，这些发现表明免疫细胞中胰岛素信号的失调可能是与糖尿病相关的免疫病理学的一个促成因素。从机制上讲，胰岛素通过激活 PI3K/Akt/mTOR 通路，调节骨髓细胞和淋巴细胞的各个方面，例如细胞存活、代谢重编程以及免疫细胞的极化和分化。PI3K 信号传导也被免疫检查点蛋白抑制，这表明胰岛素信号传导可能拮抗外周耐受。值得注意的是，最近还表明，在胰岛素结合后，胰岛素受体转移到细胞核，在那里它在调节各种免疫相关基因的转录中起关键作用，包括参与病毒感染的途径。总之，这些观察结果表明，失调的胰岛素信号传导可能直接导致 COVID-19 感染期间的免疫反应缺陷。胰岛素受体转移到细胞核，在那里它在调节各种免疫相关基因的转录中发挥关键作用，包括参与病毒感染的途径。总之，这些观察结果表明，失调的胰岛素信号传导可能直接导致 COVID-19 感染期间的免疫反应缺陷。胰岛素受体转移到细胞核，在那里它在调节各种免疫相关基因的转录中发挥关键作用，包括参与病毒感染的途径。总之，这些观察结果表明，失调的胰岛素信号传导可能直接导致 COVID-19 感染期间的免疫反应缺陷。