Insulin regulation of the glucagon gene is mediated by an insulin-responsive DNA element.
Diabetes mellitus is characterized by insulin deficiency and high plasma glucagon levels, which can be normalized by insulin replacement. It has previously been reported that glucagon gene expression is negatively regulated by insulin at the transcriptional level. By transfection studies, I have now localized a DNA control element that mediates insulin effects on glucagon gene transcription. This element also confers insulin responsiveness to a heterologous promoter. DNA-binding proteins that specifically interact with this insulin-responsive element are found in both glucagon- and non-glucagon-producing cells; and the pattern of binding, as assessed by the gel retardation assay, is not modified by prior insulin treatment.
Philippe
J
J
Department of Microbiology, Centre Médical Universitaire, Geneva, Switzerland.
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002872:Chromosome Deletion; D015870:Gene Expression / Q000187:drug effects; D005934:Glucagon / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D018139:Simplexvirus / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D014162:Transfection
D007328:Insulin; D015345:Oligonucleotide Probes; D011994:Recombinant Proteins; D005934:Glucagon; D015500:Chloramphenicol O-Acetyltransferase; D013937:Thymidine Kinase