Background and Aims:

Cardiovascular disease (CVD) is the leading cause of death in adults with type 2 diabetes (T2D). Elevated LDL (low-density lipoprotein) cholesterol that promotes atherosclerosis, which is treated through a combination of statins and diet. Statins are very effective for lipid lowering, but new clinical studies show that some statins increase risk for T2D. Our objective was to study the effects of different statins (simvastatin and pitavastatin) on insulin content and glucose-stimulated insulin secretion (GSIS) in β-cells.

Methods:

We performed in vitro studies of clonal pancreatic beta-cells (INS-1 832/13) under diabetic conditions (4mM and 11 mM glucose). Statins were added to cultures 72 hours prior to GSIS and insulin content measurements. GSIS was quantified after 2 hr preincubation at low glucose (2 mM glucose) and insulin content measured after lysing cells. Insulin release was measured using an HTRF insulin assay (CisBio, Bedford, MA). All experiments were performed at least three times. Data was analyzed via t-test. * = p<0.05.

Results

Simvastatin dose-dependently reduced insulin content and GSIS. When secretion data was normalized to insulin content, the inhibitory effect was not observed. In contrast, pitavastatin did not inhibit GSIS significantly at any study dose, and insulin content was not significantly different from controls.

Conclusions:

The results from our studies revealed cellular mechanisms that could raise plasma glucose and explain the differential risk and interference in glucose regulation between different statins. Additional studies will contribute to optimizing individual patient treatment.

02 - EFFECTS OF DIFFERENT STATINS ON INSULIN STORAGE AND SECRETION FROM PANCREATIC Β-CELLS: MECHANISMS AND CLINICAL IMPLICATIONS.