The gene for hepatocyte nuclear factor (HNF)-4 alpha is activated by glucocorticoids and glucagon, and repressed by insulin in rat liver

The gene for a transcription factor hepatocyte nuclear factor-4 alpha (HNF- 4 alpha) is responsible for maturity-onset diabetes of the young, type 1, W e examined hormonal regulation of the HNF-4 alpha gene in the liver. Stimul ation of primary-cultured rat hepatocytes with dexamethasone or glucagon le d to induction of HNF-4 alpha mRNA, being antagonized by insulin. In the li ver of streptozotocin-induced diabetic rat, mRNA and protein levels for HNF -4 alpha were elevated, and were normalized by insulin treatment, Therefore , HNF-4 alpha in the liver is likely to be involved in the regulation of gl ucose metabolism in response to these hormones, (C) 2000 Federation of Euro pean Biochemical Societies, Published by Elsevier Science B.V. All rights r eserved.