IDE (Insulin Degrading Enzyme): Insulin & Glucose

Glucose inhibits the insulin-induced activation of the insulin-degrading enzyme in HepG2 cells

This was an in vitro study done with human liver cells (HepG2 cell line).  The cells were incubated with either a normal glucose solution (1g/L = 100 mg/dL common units for blood glucose) or a high glucose solution (4.5g/L = 450 mg/dL) and treated with insulin for 24 hours vs. untreated cells.  The activity of insulin degrading enzyme, IDE, was measured.  (For those not familiar with IDE, here's the Wikipedia entry on it)

Here are the results for one insulin concentration studied: (as always you can click to enlarge)

Note:  cytosol = fluid inside the cells

So we see that at normal glucose levels insulin markedly stimulates IDE inside the cells while mildly suppressing it in the membrane.  The total effect is a marked stimulation of IDE by insulin.  This effect is almost nullified by hyperglycemia with an insignificant uptick in cytosolic activity and an uptick in membrane activity for only a small total stimulatory effect.

The observed increase in IDE activity after insulin treatment in human hepatoma cells under normal glucose concentration obviously switches off the action of insulin:  insulin induces an increase in IDE activity which leads to increased insulin degradation and decreased insulin signalling.

Insulin stimulates its own proper degradation and disposal under normal conditions.  

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