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Everolimus Directly Suppresses Insulin Secretion Independently of Cell Growth Inhibition. | LitMetric

AI Article Synopsis

  • Everolimus is a drug used for both cancer treatment and to prevent organ rejection, which can also affect insulin secretion in patients with insulinoma.
  • A clinical case showed that serum insulin levels in a patient with metastatic insulinoma changed significantly after stopping and restarting everolimus, indicating its influence on insulin secretion.
  • Laboratory experiments further confirmed that everolimus directly suppresses insulin secretion from certain cells, suggesting its effects go beyond just reducing tumor size.

Article Abstract

Everolimus, an orally administered mammalian target of rapamycin inhibitor, has been widely used as an immunosuppressant and an anticancer agent. Whereas everolimus can control recurrent hypoglycemia in patients with insulinoma, possibly through tumor regression and/or the direct inhibition of insulin secretion, time-dependent changes in serum insulin levels caused by everolimus still remain unclear. Here we report a clinical case of a patient with metastatic insulinoma, in which frequent monitoring of serum insulin levels demonstrated rapid and substantial changes in insulin secretion levels, a few days after the discontinuation as well as the readministration of everolimus. To further confirm the direct effect of everolimus on -cell function, we performed experiments using mouse insulinoma cells (MIN6) and human induced pluripotent stem cell (hiPSC)-derived insulin-producing cells and found that everolimus significantly suppressed glucose-stimulated insulin secretion in both MIN6 cells and hiPSC-derived insulin-producing cells. Thus, both a patient with metastatic insulinoma and experiments demonstrated that everolimus directly suppresses insulin secretion, independently of its tumor regression effect.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007247PMC
http://dx.doi.org/10.1210/js.2017-00475DOI Listing

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