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Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity

Shi-Bing Yang1, Hye Young Lee, David Matthew Young

  • 1Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco, 1550, 4th Street, San Francisco, CA 94158, USA.

Journal of Molecular Medicine (Berlin, Germany)
|November 23, 2011
PubMed

Insights

Rapamycin, an mTOR inhibitor, impairs glucose homeostasis and insulin secretion in mice. Chronic rapamycin treatment may be diabetogenic, necessitating glucose monitoring for therapeutic use.

Area of Science:

  • Gerontology
  • Metabolic disease research
  • Pharmacology

Background:

  • Rapamycin (mTORC1 inhibitor) is FDA-approved for immunosuppression.
  • Rapamycin shows potential for anti-cancer, anti-diabetic, and anti-aging applications.
  • Understanding rapamycin's impact on glucose metabolism is critical.

Purpose of the Study:

  • To investigate the effects of rapamycin treatment on glucose homeostasis.
  • To determine if rapamycin impacts insulin secretion, beta cell function, and insulin sensitivity.

Main Methods:

  • Administered rapamycin to aged and lean C57B/L6 mice.
  • Assessed glucose homeostasis, glucose-stimulated insulin secretion (in vivo and ex vivo).
  • Measured insulin content, beta cell mass, and insulin sensitivity.

Main Results:

  • Rapamycin treatment significantly impaired glucose homeostasis in aged mice.
  • Reduced glucose-stimulated insulin secretion, insulin content, and beta cell mass in lean mice.
  • Decreased insulin sensitivity, contributing to overall glucose intolerance.

Conclusions:

  • Chronic rapamycin treatment can be diabetogenic.
  • Rapamycin negatively affects multiple aspects of glucose metabolism.
  • Monitoring glucose homeostasis is essential when using rapamycin therapeutically or experimentally.

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