Immunity:病毒感染可恶化前驱糖尿病

创作:女巫 审核:李丹宜 2018年07月12日
在小鼠和人中病毒感染可引起短期全身性胰岛素抵抗(IR);
病毒诱导的干扰素-γ下调骨骼肌胰岛素受体表达,肌肉IR导致代偿性高胰岛素血症以维持血糖正常;
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;
病毒感染导致具有肝IR的肥胖小鼠快速进展为糖尿病;
遭遇病原体后,免疫系统会短暂降低骨骼肌的胰岛素敏感性,从而诱发高胰岛素血症并促进抗病毒免疫,使患有前驱糖尿病的肥胖个体发生葡萄糖不耐受。
延伸阅读
Immunity [IF:19.734]

Virus-Induced Interferon-γ Causes Insulin Resistance in Skeletal Muscle and Derails Glycemic Control in Obesity

病毒诱导的干扰素-γ导致骨骼肌胰岛素抵抗和破坏肥胖症中的血糖控制

2018-06-20, Article, 10.1016/j.immuni.2018.05.005more

Abstract:
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.

First Authors:
Sonja Marinović,Inga Kavazović

Correspondence Authors:
Bojan Polić

All Authors:
Marko Šestan,Sonja Marinović,Inga Kavazović,Đurđica Cekinović,Stephan Wueest,Tamara Turk Wensveen,Ilija Brizić,Stipan Jonjić,Daniel Konrad,Felix M Wensveen,Bojan Polić