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Mol Med Rep ; 18(3): 2780-2788, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30015940

ABSTRACT

Low­density lipoprotein receptors (LDLRs) may serve a role in the diabetogenic effect of statins; however, the effects of statins on LDLR expression and its regulation in the pancreas and islets have yet to be determined. To exclude the long­term effects of treatment with atorvastatin, which allows mice to adapt, male C57BL/j and apolipoprotein E­deficient mice were acutely treated with oral atorvastatin for 6 weeks, and glucose homeostasis and LDLR expression in the pancreas and islets were examined. In the present study, it was observed that the short­term use of atorvastatin affected insulin sensitivity in normal mice and glucose tolerance in hyperlipidemic mice. Furthermore, it was identified that 6 weeks of treatment with atorvastatin suppressed LDLR expression in the pancreas and pancreatic islets in C57BL/j mice, and an increase in proprotein convertase subtilisin/kexin type 9 expression was additionally observed in the pancreas. However, 6 weeks of treatment with atorvastatin did not affect LDLR expression in the pancreas of hyperlipidemic mice. It may be concluded that the short­term use of atorvastatin disturbs glucose homeostasis and suppresses LDLR expression in the pancreas and pancreatic islets in C57BL/j mice, suggesting that the role of LDLR in the diabetogenic effect of statins requires further investigation.


Subject(s)
Atorvastatin/pharmacology , Down-Regulation/drug effects , Glucose/metabolism , Islets of Langerhans/metabolism , Receptors, LDL/metabolism , ATP Binding Cassette Transporter 1/genetics , ATP Binding Cassette Transporter 1/metabolism , Animals , Cells, Cultured , Hyperlipidemias/metabolism , Hyperlipidemias/pathology , Hyperlipidemias/veterinary , Islets of Langerhans/cytology , Lipids/blood , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Proprotein Convertase 9/blood , Proprotein Convertase 9/genetics , Proprotein Convertase 9/metabolism , Receptors, LDL/genetics , Sterol Regulatory Element Binding Protein 2/genetics , Sterol Regulatory Element Binding Protein 2/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism
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