As the liver is a major site of glucocorticoid action on metabolic homeostasis regulated by the glucocorticoid receptor, we have assessed how different patterns of hormone replacement in adrenalectomised rats differentially regulate gene pathways involved in type II diabetes, cirrhosis, and fatty liver development, via altering the pattern of glucocorticoid receptor binding to regulatory sites. Here, NR3C1 is linked to type 2 diabetes mellitus.