Glucocorticoid-induced Insulin Resistance

It is well established that in the clinic, oversecretion of glucocorticoids (eg in Cushing’s syndrome) can produce insulin resistance. This has led to the development of glucocorticoid-induced insulin secretion in rats and mice as a screen for potential antidiabetic activity. In brief, repeated administration of a glucocorticoid such as cortisone once a day for 4 days significantly increased plasma insulin levels and produced modest increases in plasma glucose. This model is particularly sensitive to inhibitors of 11β hydroxysteroid dehydrogenase (11βHSD), enzymes which catalyze the conversion of cortisone to cortisol (and vice versa) and therefore regulate the access of glucocorticoids to steroid receptors.