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

FEBS Lett. 2000 Jul 28;478(1-2):141-6. doi: 10.1016/s0014-5793(00)01840-8.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • DNA-Binding Proteins*
  • Dexamethasone / antagonists & inhibitors
  • Dexamethasone / pharmacology*
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / metabolism
  • Gene Expression Regulation / drug effects*
  • Glucagon / antagonists & inhibitors
  • Glucagon / pharmacology*
  • Glucose / metabolism
  • Hepatocyte Nuclear Factor 4
  • Insulin / pharmacology*
  • Insulin Antagonists / pharmacology
  • Liver / cytology
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptional Activation / drug effects

Substances

  • DNA-Binding Proteins
  • Hepatocyte Nuclear Factor 4
  • Insulin
  • Insulin Antagonists
  • Phosphoproteins
  • RNA, Messenger
  • Transcription Factors
  • Dexamethasone
  • Glucagon
  • Glucose