Cytokine resistance contributes to pathology of type ...( itol-3 kinase (IRS-2/PI3K) pathway was...)

What drew them to this pathway was its potential role in the anti-inflammatory response, and its similarity to the cascade initiated when cells respond to insulin.

One of the actions of diabetes is to create intracellular insulin resistance, Freund said. Some of the cytokines that work on cells share the same pathways as the insulin receptor. Since diabetes causes insulin resistance, Freund said, shouldnt there be a resistance to cytokines, too" And that is what we found.

The research team showed, for the first time, that the IRS-2 signaling arm of the interleukin-4 pathway directed the up-regulation of a key anti-inflammatory molecule in primary macrophages, and that this pathway was disrupted in type 2 diabetic conditions. They also showed that the loss of IL-4 function in diabese mice caused chronic over-expression of an important suppressor of cytokine signaling (SOCS) protein. This SOCS-3 protein aborts the cascade of events that normally leads to insulin uptake and/or cytokine signaling in a balanced inflammatory response.

This study supports earlier findings that inflammation is a key part of the pathology of diabetes, Freund said. Pro-inflammatory cytokines are elevated in type 2 diabetes, but the anti-inflammatory mechanisms are also impaired, leading to a multitude of major and minor health issues in the diabese.

They get a cold. They get injured. Something happens. And its worse in those people with obesity or diabetes and lasts longer than it does in others, Freund said. Why" The imbalance may be the elevation in pro-inflammation. But it probably also includes a loss of anti-inflammatory function.

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Contact: Diana Yates
diya@uiuc.edu
217-333-5802
University of Illinois at Urbana-Champaign
14-Jun-2007