Coenzyme Q 10 protects against β-cell toxicity induced by pravastatin treatment of hypercholesterolemia

• Published in: Journal of cellular physiology Vol. 234; no. 7; pp. 11047 - 11059
• Main Authors: Lorza-Gil, Estela, de Souza, Jane C, García-Arévalo, Marta, Vettorazzi, Jean F, Marques, Ana Carolina, Salerno, Alessandro G, Trigo, Jose Roberto, Oliveira, Helena C F
• Format: Journal Article
• Language: English
• Published: United States 01-07-2019
• Subjects: Animals; Cell Line; Cell Survival; Diabetes Mellitus - chemically induced; Dietary Supplements; Female; Glucose Tolerance Test; Hydrogen Peroxide; Hypercholesterolemia - drug therapy; Insulin; Insulin-Secreting Cells - drug effects; Liver - metabolism; Mice; Mice, Knockout; Pravastatin - adverse effects; Pravastatin - therapeutic use; Receptors, LDL - genetics; Receptors, LDL - metabolism; Ubiquinone - analogs & derivatives; Ubiquinone - pharmacology; β cell; coenzyme Q10; cell death; insulin; statins
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.27932

New onset of diabetes is associated with the use of statins. We have recently demonstrated that pravastatin-treated hypercholesterolemic LDL receptor knockout (LDLr
) mice exhibit reductions in insulin secretion and increased islet cell death and oxidative stress. Here, we hypothesized that these diabetogenic effects of pravastatin could be counteracted by treatment with the antioxidant coenzyme Q
(CoQ
), an intermediate generated in the cholesterol synthesis pathway. LDLr
mice were treated with pravastatin and/or CoQ
for 2 months. Pravastatin treatment resulted in a 75% decrease of liver CoQ
content. Dietary CoQ
supplementation of pravastatin-treated mice reversed fasting hyperglycemia, improved glucose tolerance (20%) and insulin sensitivity (>2-fold), and fully restored islet glucose-stimulated insulin secretion impaired by pravastatin (40%). Pravastatin had no effect on insulin secretion of wild-type mice. In vitro, insulin-secreting INS1E cells cotreated with CoQ
were protected from cell death and oxidative stress induced by pravastatin. Simvastatin and atorvastatin were more potent in inducing dose-dependent INS1E cell death (10-15-fold), which were also attenuated by CoQ
cotreatment. Together, these results demonstrate that statins impair β-cell redox balance, function and viability. However, CoQ
supplementation can protect the statins detrimental effects on the endocrine pancreas.