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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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Cells, Cultured
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DNA-Binding Proteins*
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Dexamethasone / antagonists & inhibitors
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Dexamethasone / pharmacology*
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Diabetes Mellitus, Experimental / chemically induced
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Diabetes Mellitus, Experimental / genetics
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Diabetes Mellitus, Experimental / metabolism
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Gene Expression Regulation / drug effects*
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Glucagon / antagonists & inhibitors
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Glucagon / pharmacology*
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Glucose / metabolism
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Hepatocyte Nuclear Factor 4
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Insulin / pharmacology*
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Insulin Antagonists / pharmacology
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Liver / cytology
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Liver / drug effects*
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Liver / metabolism
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Liver / pathology
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Male
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Phosphoproteins / genetics*
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Phosphoproteins / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transcriptional Activation / drug effects
Substances
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DNA-Binding Proteins
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Hepatocyte Nuclear Factor 4
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Insulin
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Insulin Antagonists
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Phosphoproteins
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RNA, Messenger
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Transcription Factors
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Dexamethasone
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Glucagon
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Glucose