Differential effects of statins on the pancreatic beta cell
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Statins are widely used in the treatment of atherosclerosis and hypercholesterolemia, both of which are comorbidities of obesity. However, the effects statins have on insulin homeostasis are relatively unknown and may increase one’s risk for type-II diabetes mellitus. INS-1 pancreatic β-cells, were cultured in 11 mM glucose with 25, 50, 100, 200 nM statin or without. Specifically, this study observed the effects that pitavastatin, simvastatin, lovastatin, and pravastatin have on insulin secretion, insulin content, and ROS levels. GSIS was measured after statin and non-statin exposed cells were incubated in 12 mM glucose KRB. Insulin content was measured after trypsinization and subsequent lysing of cells. Both were analyzed via FRET based HTRF assay. ROS levels within cells were measured following statin exposure during a 2-hour period of 12 mM glucose oxidation after DCF was added. Analysis was done using a Tecan™ fluorescent microplate reader. Pitavastatin, simvastatin, and lovastatin decrease glucose stimulated insulin secretion and insulin content as compared to control. All concentrations of pitavastatin reduced insulin secretion proportionally to insulin content, suggesting it does so through impairment of insulin synthesis or storage. Simvastatin reduced insulin secretion and content in a dose dependent manner, however when secretion was adjusted for % content, data showed that high doses of simvastatin reduced insulin content in a greater fashion than insulin secretion, suggesting both secretory mechanisms and storage/synthesis were impaired. Lovastatin reduced insulin secretion by a greater amount than its reduction of insulin content, suggesting that it impaired insulin secretion via secretory mechanism impairment. Pravastatin did not have an effect on either insulin secretion or insulin content at any concentration. Cells were also tested to determine if pitavastatin, simvastatin, or lovastatin induced a change in ROS levels within the cell. None of the three statins tested caused a statistically significant change in ROS levels at all concentrations. These results suggest that pitavastatin, simvastatin, and lovastatin may impair insulin secretion in patients with high blood glucose. As such, clinical guidelines for statin therapy use in those who are at risk, or suffer from, diabetes may need to be reevaluated.