Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Department of Infectology, Clinical Hospital Center Rijeka, Rijeka, Croatia.
Immunity. 2018 Jul 17;49(1):164-177.e6. doi: 10.1016/j.immuni.2018.05.005. Epub 2018 Jun 26.
Pro-inflammatory cytokines of a T helper-1-signature are known to promote insulin resistance (IR) in obesity, but the physiological role of this mechanism is unclear. It is also unknown whether and how viral infection induces loss of glycemic control in subjects at risk for developing diabetes mellitus type 2 (DM2). We have found in mice and humans that viral infection caused short-term systemic IR. Virally-induced interferon-γ (IFN-γ) directly targeted skeletal muscle to downregulate the insulin receptor but did not cause loss of glycemic control because of a compensatory increase of insulin production. Hyperinsulinemia enhanced antiviral immunity through direct stimulation of CD8 effector T cell function. In pre-diabetic mice with hepatic IR caused by diet-induced obesity, infection resulted in loss of glycemic control. Thus, upon pathogen encounter, the immune system transiently reduces insulin sensitivity of skeletal muscle to induce hyperinsulinemia and promote antiviral immunity, which derails to glucose intolerance in pre-diabetic obese subjects. VIDEO ABSTRACT.
已知辅助性 T 细胞 1 型细胞因子可促进肥胖者的胰岛素抵抗（IR），但其发生机制尚不清楚。此外，尚不清楚病毒感染是否以及如何导致 2 型糖尿病（DM2）高危人群血糖控制丧失。我们在小鼠和人类中发现，病毒感染可导致短期系统性 IR。病毒诱导的干扰素-γ（IFN-γ）直接靶向骨骼肌，下调胰岛素受体，但由于胰岛素产生代偿性增加，不会导致血糖控制丧失。高胰岛素血症通过直接刺激 CD8 效应 T 细胞功能增强抗病毒免疫。在由饮食诱导肥胖引起的肝胰岛素抵抗的糖尿病前期小鼠中，感染导致血糖控制丧失。因此，在病原体入侵时，免疫系统会短暂降低骨骼肌对胰岛素的敏感性，以诱导高胰岛素血症并促进抗病毒免疫，从而导致糖尿病前期肥胖患者的葡萄糖不耐受。视频摘要。
