Over-secretion of glucocorticoids (e.g. in Cushing’s syndrome) can produce insulin resistance in the clinic. This has led to the development of glucocorticoid-induced insulin resistance in rats and mice as a screen for potential antidiabetic activity.

 

We have shown that sub-chronic administration of a glucocorticoid such as cortisone once a day significantly increased plasma glucose and insulin levels in rats. This model can be used to evaluate the antidiabetic potential of novel drugs such as selective glucocorticoid antagonists, or inhibitors of 11β hydroxysteroid dehydrogenase (11βHSD). These enzymes catalyse the conversion of cortisone to cortisol (and vice versa), and therefore regulate the access of glucocorticoids to steroid receptors.

 

Effect of CORT12534, CORT108297 and mifepristone on body weight,
plasma glucose and insulin in male Sprague Dawley rats

 

Data are adjusted means + SEM (n = 8). Significant differences vs. vehicle only: **p<0.01 ***p<0.001. Significant differences vs. cortisone + vehicle: ###p<0.001.

 

Data are adjusted means + SEM (n = 8). Significant differences vs. vehicle only: **p<0.01 ***p<0.001. Significant differences vs. cortisone + vehicle: ###p<0.001.

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