[Relationship between insulin-degrading enzyme activity and insulin sensitivity in cell model of insulin-resistance].

OBJECTIVE

To investigate the relationship between insulin-degrading enzyme (IDE) activity and the onset and development of insulin resistance (IR).

METHODS

Rat primary hepatocytes with IR induced by high concentration of human insulin were used in which the incorporation rates of 14C-2-deoxyglucose and 14C-acetate were determined to estimate the insulin sensitivity of the cells and IDE activity was assessed. The effects of IDE inhibitor, chloroquine, and IDE activator, iodoacetamide, on these indices were observed.

RESULTS

IDE activity of IR cells was increased, and 14C-2-deoxyglucose and 14C-acetate incorporation rates were decreased as compared with the control cells. Significant inverse correlation was observed between IDE activity of IR cells and the incorporation rates of 14C-2-deoxyglucose and 14C-acetate. Iodoacetamide resulted in increase in IDE activity and decrease in the incorporation rates while chloroquine acted to the reverse effects.

CONCLUSIONS

Increased IDE activity may be one of the mechanisms of IR genesis in rat primary hepatocytes cultured with high concentration of IDE, chloroquine, on the other hand, may ameliorate insulin sensitivity by inhibiting accelerated insulin degradation.