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

Gondwanaland

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http://sci-hub.tw/10.1016/j.immuni.2018.05.005
Immunity VOLUME 49, ISSUE 1, P164-177.E6, JULY 17, 2018

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

Published:June 26, 2018

Highlights
  • Virus-induced IFN-γ downregulates insulin receptor expression of skeletal muscle
  • Muscle insulin resistance results in compensatory hyperinsulinemia to keep euglycemia
  • Insulin directly boosts anti-viral effector CD8 + T cell responses
  • In obese mice with hepatic IR, viral infection causes rapid progression to diabetes

Summary
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.
 

Gondwanaland

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@Gondwanaland

What connections to ME are you thinking about? My brain is too tired to focus right now.

RWP
Our viral infections might be inducing diabetes symptoms, for instance:

https://forums.phoenixrising.me/ind...duced-type-i-diabetes-in-a-mouse-model.56227/

https://forums.phoenixrising.me/ind...ert-illnesses-and-subclinical-symptoms.58371/

Those who can tolerate a low carb or ketogenic diets improve:
https://forums.phoenixrising.me/index.php?threads/first-time-in-remission-with-ketogenic-diet.60886/