Diabetes alters LDL receptor and PCSK9 expression in rat liver.
Since the hepatic LDL receptor is regarded as a major determinant of plasma LDL levels, the effect of diabetes on the expression of this receptor was examined in rat liver. Inducing diabetes with streptozotocin caused a significant reduction in hepatic LDL receptor mRNA levels in concert with an increase in serum cholesterol levels. However, LDL receptor protein levels were unaffected by the diabetic state. Further investigation revealed that protein levels of PCSK9, which has been shown to enhance the degradation of the LDL receptor protein, were significantly decreased in the diabetic rats explaining the lack of reduction in LDL receptor protein levels. These observations indicate that the rate of LDL receptor cycling (function) in diabetic rats is decreased resulting in higher serum LDL levels.
Department of Molecular Medicine, School of Basic Biomedical Sciences, University of South Florida, College of Medicine, Tampa, FL 33612, USA.
Melissa
M
Niesen
Mohini
M
Bedi
Dayami
D
Lopez
D000818:Animals; D002784:Cholesterol / Q000097:blood*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism*; D008297:Male; D000071449:Proprotein Convertase 9; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D013311:Streptozocin
D011973:Receptors, LDL; D013311:Streptozocin; D002784:Cholesterol; C510804:PCSK9 protein, rat; D000071449:Proprotein Convertase 9; D012697:Serine Endopeptidases