News

I am proud to say that our latest manuscript has finally been published in the world-leading journal Nature Immunology!

First authors Marko Šestan and Sanja Mikašinović, together with our collaborators in Croatia and abroad have generated a study in which we explored the impact of infection on blood glucose regulation. In this manuscript we show that viral infection can cause a sugar crash: a drop in blood glucose levels. The purpose of this mechanism is to change systemic metabolism and make cells more responsive to viral infection. Importantly, when this mechanism was blocked in models for type 1 and type 2 diabetes, detection of virus was impaired and viral loads were increased. Šestan and Mikašinović thus uncovered why it is beneficial to feel low on energy when you are sick; it helps you better fight infection.

What we observed is that in mice (and in a pilot study we found this also in people), when the infection is strong enough, blood sugar levels drop to a minimum baseline. This happens when the virus penetrates deep into the spleen and reaches an immune cell population called γδ (gamma-delta) T cells. These cells function as ‘tripwires’: when they get activated they produce large amounts of the immunological hormone (cytokine) Interferon gamma (IFNγ). IFNγ directly targets pancreatic beta cells to produce more insulin. As you know, the role of insulin is to lower blood sugar levels and this is what happens during infection.

Of course, this is how it happens, but the question was why. What we found is that, when systemic availability of glucose is reduced, cells in the body change how they metabolize glucose to generate energy. Instead of using the relatively inefficient glycolysis, a process producing lactate, they increase respiratory metabolism, which generates more energy per molecule of glucose and no lactate. Lactate is a natural inhibitor of a viral detection system that is present in every cell and results in the production of an alarm signal: the cytokine interferon-beta (IFNβ). IFNβ is crucial for the early anti-viral response. In summary, by lowering systemic glucose upon infection, cells in the body make less lactate, bringing them into a ‘heightened state of awareness’, if you will. This allows them to react stronger to viral infection and produce more IFNβ, thus limiting viral replication.

Finally, why is this important to know? Well, diabetes is an increasingly common disease and is characterized by high blood sugar levels. Also, these people have more frequent and severe infections. We investigated whether high glucose levels in his condition disrupts our anti-viral detection system. Using models for type 1 and type 2 diabetes, we caused hyperglycemia in mice and subsequently infected them with virus. Indeed, we found that these animals had lower IFNβ and higher viral titers.

Read the paper in full here: https://lnkd.in/ecwBhQyP

Or here: https://lnkd.in/ePThFm4V 

Also, check out our new website here: The Turk Wensveen Lab | Translational Medicine Rijeka (transmedri.hr)