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Everolimus Directly Suppresses Insulin Secretion Independently of Cell Growth Inhibition

Luka Suzuki1, Takeshi Miyatsuka1, Miwa Himuro1

  • 1Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Journal of the Endocrine Society
|June 27, 2018
PubMed

Insights

Everolimus, a mTOR inhibitor, directly suppresses insulin secretion in insulinoma patients and cells. This finding clarifies its role in managing hypoglycemia beyond tumor regression.

Area of Science:

  • Endocrinology
  • Pharmacology
  • Oncology

Background:

  • Everolimus (mTOR inhibitor) is used for immunosuppression and cancer.
  • It manages hypoglycemia in insulinoma, but its effect on insulin secretion timing is unclear.
  • Potential mechanisms include tumor regression and direct insulin secretion inhibition.

Purpose of the Study:

  • To investigate the time-dependent effects of everolimus on serum insulin levels in metastatic insulinoma.
  • To confirm the direct impact of everolimus on pancreatic beta-cell function.
  • To elucidate the mechanism of everolimus in controlling hypoglycemia.

Main Methods:

  • Clinical case study with frequent monitoring of serum insulin levels.
  • In vitro experiments using mouse insulinoma (MIN6) cells.
  • In vitro experiments using human induced pluripotent stem cell (hiPSC)-derived insulin-producing cells.

Main Results:

  • Observed rapid, substantial changes in serum insulin levels following everolimus discontinuation and re-administration in a patient.
  • Demonstrated significant suppression of glucose-stimulated insulin secretion in MIN6 cells.
  • Confirmed suppression of glucose-stimulated insulin secretion in hiPSC-derived insulin-producing cells.

Conclusions:

  • Everolimus directly suppresses insulin secretion from pancreatic beta-cells.
  • This direct effect is independent of tumor regression.
  • Provides a clearer understanding of everolimus's mechanism in managing insulinoma-related hypoglycemia.
Keywords:
everolimushypoglycemiainsulin secretioninsulinomamTOR inhibitor

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