Attenuation of hepatic expression and secretion of selenoprotein P by metformin.
High serum selenium levels have been associated epidemiologically with increased incidence of type 2 diabetes. The major fraction of total selenium in serum is represented by liver-derived selenoprotein P (SeP). This study was undertaken to test for a hypothesized effect of hyperglycemia and the antihyperglycemic drug metformin on hepatic selenoprotein P biosynthesis. Cultivation of rat hepatocytes in the presence of high glucose concentrations (25 mmol/l) resulted in increased selenoprotein P mRNA expression and secretion. Treatment with metformin dose-dependently downregulated SeP mRNA expression and secretion, and suppressed glucocorticoid-stimulated production of SeP. Moreover, metformin strongly decreased mRNA levels of selenophosphate synthetase 2 (SPS-2), an enzyme essential for selenoprotein biosynthesis. Taken together, these results indicate an influence of metformin on selenium metabolism in hepatocytes. As selenoprotein P is the major transport form of selenium, metformin treatment may thereby diminish selenium supply to extrahepatic tissues.
Speckmann
Bodo
B
Institute for Biochemistry and Molecular Biology I, Heinrich-Heine-University, Düsseldorf, Germany.
Sies
Helmut
H
Steinbrenner
Holger
H
D000818:Animals; D002478:Cells, Cultured; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D051149:Selenoprotein P / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D005938:Glucocorticoids; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D051149:Selenoprotein P; D008687:Metformin; D005947:Glucose