Phlorizin or vanadate treatment reverses impaired expression of albumin and hepatocyte nuclear factor 1 in diabetic rats.
Diabetes decreases transcription of the albumin gene. The role of hyperglycemia in mediating this suppression of albumin gene activity is unclear. To study the effect of glucose in vivo, we treated diabetic rats with phlorizin or vanadate, two agents that ameliorate hyperglycemia without increasing the levels of circulating insulin. When glucose was normalized in diabetic rats with either agent, the hepatic levels of albumin mRNA became indistinguishable from those in nondiabetic animals. In light of our previous observation that diabetes decreases the abundance of hepatocyte nuclear factor 1 (HNF1), the predominant factor increasing albumin gene transcription, we wondered whether glucose normalization in diabetes would alter HNF1. Both the levels and DNA binding activity of HNF1 were restored to control values when phlorizin or vanadate was administered to diabetic rats. These findings suggest that hyperglycemia is integrally involved in mediating the suppression of albumin gene expression in diabetes. The effect of hyperglycemia on HNF1 suggests that glucose affects albumin expression at the level of transcription.
Barrera-Hernandez
G
G
Department of Medicine, University of Calgary, Alberta, Canada.
Wanke
I E
IE
Wong
N C
NC
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001786:Blood Glucose / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D010695:Phlorhizin / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012709:Serum Albumin / Q000096:biosynthesis*; D013489:Suppression, Genetic / Q000187:drug effects*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000302:isolation & purification; D014158:Transcription, Genetic / Q000187:drug effects; D014638:Vanadates / Q000494:pharmacology*; D017968:Vanadium Compounds / Q000494:pharmacology
D001786:Blood Glucose; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496489:Hnf1a protein, rat; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D012709:Serum Albumin; D014157:Transcription Factors; D017968:Vanadium Compounds; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D014638:Vanadates; C034028:vanadyl sulfate; D010695:Phlorhizin