Glucocorticoid-induced model of insulin resistance

We have developed a rapid model of insulin resistance induced by sub-chronic administration of the glucocorticoid, cortisone, resulting in significantly increased plasma glucose and insulin levels within 7 days in rats. This model can be used to evaluate the antidiabetic potential of novel drugs such as selective glucocorticoid receptor 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. Below is an example demonstrating inhibition of the phenotype by mifepristone and the glucocorticoid receptor antagonist CORT125134.

The glucocorticoid receptor antagonists CORT125134 and mifepristone improve cortisone-induced insulin resistance and hyperglycaemia in male Sprague Dawley rats