Diabetes mellitus decreases the activity of the albumin promoter in vitro.
Diabetes mellitus (DM) has been shown previously to decrease hepatic synthesis of both albumin and albumin mRNA. These findings prompted us to ask whether decreased albumin expression is due to changes in the rate of gene transcription. A cell-free in vitro transcription assay demonstrated that activity of the albumin promoter in hepatonuclear extracts was diminished 3- to 4-fold in diabetic compared with control animals. This decrease was abolished in extracts prepared from diabetic animals treated with insulin. The potential mechanisms for diminished activity were examined by mixing extracts from normal and diabetic animals prior to incubation with DNA templates. In the presence of limited amounts of albumin promoter DNA, addition of diabetic to control extract caused a reduction in promoter activity, suggesting that an inhibitor or inhibitors of albumin promoter activity is/are present in the liver of diabetic rats.
Wanke
I E
IE
Department of Medicine, University of Calgary, Alberta, Canada.
Wong
N C
NC
D000418:Albumins / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D004247:DNA / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D007328:Insulin / Q000494:pharmacology; D008297:Male; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D013698:Templates, Genetic; D014158:Transcription, Genetic
D000418:Albumins; D007328:Insulin; D012333:RNA, Messenger; D004247:DNA