Distinct effects of pravastatin, atorvastatin, and simvastatin on insulin secretion from a beta-cell line, MIN6 cells.
In addition to the prevention of cardiovascular diseases by lowering plasma LDL cholesterol, recent studies suggest that statins could have some impact on insulin action. To estimate the direct effects of statins on insulin secretion from pancreatic beta-cells, MIN6 cells were treated with pravastatin, simvastatin, or atorvastatin. Basal insulin secretion at low glucose concentration was unexpectedly increased at very high doses of simvastatin or atorvastatin after 24- and 48-hour incubation. Insulin secretion at high glucose was not significantly changed, and thus, net glucose-stimulated insulin secretion was apparently decreased by these lipophilic statins. The changes in insulin secretion were highly associated with increased endogenous SREBP activities in response to HMG-CoA inhibition as estimated by SRE-luciferase assays, and finally after 48-hour incubation, accompanied by impaired cell viability as estimated by MTT assays. In contrast, these changes were much less prominent by the addition of pravastatin. Meanwhile, glucose-stimulated insulin secretion of islets isolated from C57BL/6 mice was not significantly changed by any of the statins. Overall, taken up by beta-cells, statins can affect insulin secretion through either HMG-CoA inhibition or cytotoxicity, as observed by the addition of extraordinary high doses of lipophilic statins, but not hydrophilic statins, to the medium.
Ishikawa
Mayumi
M
Department of Internal Medicine (Endocrinology and Metabolism) Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
Okajima
Fuminori
F
Inoue
Noriyuki
N
Motomura
Kaori
K
Kato
Toyonori
T
Takahashi
Akimitsu
A
Oikawa
Shinichi
S
Yamada
Nobuhiro
N
Shimano
Hitoshi
H
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006538:Heptanoic Acids / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017035:Pravastatin / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D019821:Simvastatin / Q000494:pharmacology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000187:drug effects / Q000378:metabolism
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D011758:Pyrroles; D051780:Sterol Regulatory Element Binding Protein 1; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin