Chronic use of pravastatin reduces insulin exocytosis and increases β-cell death in hypercholesterolemic mice

Highlights • Hypercholesterolemic mice have reduced insulin secretion. • We hypothesized that pravastatin treatment improves insulin secretion. • Pravastatin chronic treatment impaired glucose stimulated insulin secretion. • Pravastatin also decreased the expression of exocytotic SNARE proteins. • P...

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Veröffentlicht in:	Toxicology (Amsterdam) 2016-02, Vol.344, p.42-52
Hauptverfasser:	Lorza-Gil, Estela, Salerno, Alessandro G, Wanschel, Amarylis C.B.A, Vettorazzi, Jean F, Ferreira, Mônica S, Rentz, Thiago, Catharino, Rodrigo R, Oliveira, Helena C.F
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Apoptosis Cholesterol Diabetes Drug Administration Schedule Emergency Exocytosis - drug effects Exocytosis - physiology Female Glucose Hydroxymethylglutaryl-CoA Reductase Inhibitors - toxicity Hypercholesterolemia - genetics Hypercholesterolemia - metabolism Hypercholesterolemia - pathology Insulin Insulin - metabolism Insulin secretion Insulin-Secreting Cells - drug effects Insulin-Secreting Cells - metabolism Insulin-Secreting Cells - pathology LDL receptor Markers Mice Mice, Inbred C57BL Mice, Knockout Pravastatin - toxicity Proteins Receptors, LDL - deficiency Receptors, LDL - genetics Secretions SNARE proteins Statins
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Zusammenfassung:	Highlights • Hypercholesterolemic mice have reduced insulin secretion. • We hypothesized that pravastatin treatment improves insulin secretion. • Pravastatin chronic treatment impaired glucose stimulated insulin secretion. • Pravastatin also decreased the expression of exocytotic SNARE proteins. • Pravastatin induced apoptosis signaling and death rates in pancreatic islets.
ISSN:	0300-483X 1879-3185
DOI:	10.1016/j.tox.2015.12.007