The gene for a transcription factor hepatocyte nuclear factor-4α (HNF-4α) is responsible for maturity-onset diabetes of the young, type 1. We examined hormonal regulation of the HNF-4α gene in the liver. Stimulation of primary-cultured rat hepatocytes with dexamethasone or glucagon led to induction of HNF-4α mRNA, being antagonized by insulin. In the liver of streptozotocin-induced diabetic rat, mRNA and protein levels for HNF-4α were elevated, and were normalized by insulin treatment. Therefore, HNF-4α in the liver is likely to be involved in the regulation of glucose metabolism in response to these hormones.
