Direct Effects of Different Statins to Glucose Stimulated Pancreatic Beta Cell Function

Presentation Number: SAT 584
Date of Presentation: April 1st, 2017

Su Kyoung Kwon*1, Jeonghoon Heo2, Jeonghyun Lee1, Shin Jun Lee3, So Young Ock1, Bu Kyung Kim1 and Young-Sik Choi4
1Kosin University College of Medicine, Busan, Korea, Republic of (South), 2Kosin University College of Medicine, 3Kosin University Gospel Hospital, Busan, Korea, Republic of (South), 4Kosin Univ Sch of Med, Busan, Korea, Republic of (South)

Abstract

Objective: Increased risk of diabetes has been suggested with statin use although overall benefits of cardiovascular outcome have been observed. Detrimental effects of statin to insulin secretion in pancreatic β-cell was suggested as one of the possible mechanism of statin induced diabetes. However direct comparison or differences among diverse satins to pancreatic beta cell function associated with insulin secretion was not evaluated. This study was performed to demonstrate and compare the direct effects of different stains on β-cell function.

Methods Pancreatic β-cell line (INS-1 cells) were cultured with or without statins and normal or high glucose conditions. In treatment group, cells were cultured with different classes and doses of statins respectively containing atorvastatin, rosuvastatin, simvastatin, pitavastatin and pravastatin at 10 x, 100 x, 1,000 x IC 50 concentration estimated by HMG-CoA reductase inhibitor. The cytotoxicity was determined by MTT assay. The concentrations of insulin secreted from INS-1 cells were determined by ELISA kit and insulin mRNA expression was measured by RT-PCR.

Results: Cell viability was not affected by the 10x and 100 x IC50 concentrations of each statin, but decreased in 1,000 x IC50 concentration of atorvastatin, simvastatin and pitavastatin. In low and high glucose condition, insulin secretion was decreased in 1000 x IC50 concentration of atorvastatin, simvastatin and pitavastatin but was not affected in the concentrations of rosuvastatin and pravastatin. Glucose stimulated insulin secretion (GSIS) was decreased in 1000 x IC50 concentration of atorvastatin, simvastatin and pitavastatin but was not affected in the concentrations of rosuvastatin and pravastatin. The effects of statins on GSIS were related with decreased cell viability in 1,000 x IC50 concentration but not in cell viable concentration.

Conclusion: Atorvastatin, rosuvastatin, simvastatin, pitavastatin and pravastatin do not directly affect insulin secretion nor insulin gene expression in INS-1 cells in cell viable concentrations of each statin regardless of glucose concentration. The detrimental effects of lipophilic statins on GSIS were thought to be related with decreased cell viability in 1,000 x IC50 concentration rather than direct effect to beta cell. Direct effects of statin to inhibit insulin secretion nor gene expression to pancreatic β-cell is less likely as a main mechanism of statin induced diabetes.

 

Nothing to Disclose: SKK, JH, JL, SJL, SYO, BKK, YSC