OBJECTIVE: The 10th leading cause of death in the United States is heart disease. Most of the deaths by heart disease has a correlation with an occlusion of the coronary arteries. While diabetes mellitus is currently the 7th leading cause of death, which is a chronic condition that affects more than 37 million people in America. The global epidemic of obesity largely explains the dramatic increase in the incidence and prevalence of type 2 diabetes (T2D) over the past 25 years. Statins are well known drugs to decrease LDL for individuals who suffer from hypercholesterinemia; however, there is also an increased risk of developing diabetes mellitus. An estimation of 10-20 per 10,000 patients per year demonstrated an excess risk of T2D with the long-term use of statin. Here we examine the effects of simvastatin and pitavastatin on pancreatic ß-cell function to determine whether altered insulin secretion may contribute to an increased risk of T2D.
METHODS: The experiments were performed using clonal pancreatic ß-cells (INS-1). The cells were grown in 4 mM glucose in RPMI media. Cells were grown for three days before adding the different types of statins: simvastatin and pitavastatin for one day. Then the cells were used to perform the glucose-induced insulin secretion (GSIS) experiment. Insulin secretion and insulin content were assay using a fluorescence-based immunoassay. The study was calculated using Microsoft Excel. Standard variance and standard error were used to assess the difference sets of data.
RESULTS: INS-1 cells responded to acute glucose stimulation after chronic culture in both low (4 mM) and high (11 mM) glucose. Secretion from cells cultured at 4 mM glucose was higher than cells cultured at 11 mM glucose at all glucose concentrations tested, characteristic of the effects of glucolipotoxicity (GLT). Insulin content in cells cultured at high glucose was decreased 8.6-fold compared to cells cultured at the more physiological low glucose condition. When normalized to basal secretion cells cultured at high glucose exhibited basal hypersecretion and increased GSIS compared to those in low glucose.
Simvastatin (100 nM, 24 hrs) increased basal insulin secretion to a greater extent than Pitavastatin. The effects of pitavastatin on basal insulin secretion were less consistent than seen with simvastatin. Simvastatin was also shown to inhibit GSIS from cells cultured at 4 mM glucose, while pitavastatin increased GSIS.
CONCLUSION: Both pitavastatin and simvastatin alter insulin secretion from pancreatic ß-cells. The effect of simvastatin to both increase basal and decrease GSIS, characteristic of GLT suggests pitavastatin may be the statin of choice to reduce the risk of statin-induced T2D.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/48101 |
| Date | 13 February 2024 |
| Creators | Abdul-Akbar, Princess Maryam |
| Contributors | Deeney, Jude T., Hamilton, James |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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