MTORC1 signaling and regulation of pancreatic β-cell mass

Manuel Blandino-Rosano, Angela Y. Chen, Joshua O. Scheys, Emilyn U. Alejandro, Aaron P. Gould, Tatyana Taranukha, Lynda Elghazi, Corentin Cras-Méneur, Ernesto Bernal-Mizrachi

Research output: Contribution to journalReview article

36 Scopus citations

Abstract

The capacity of β cells to expand in response to insulin resistance is a critical factor in the development of type 2 diabetes. Proliferation of β cells is a major component for these adaptive responses in animal models. The extracellular signals responsible for β-cell expansion include growth factors, such as insulin, and nutrients, such as glucose and amino acids. AKT activation is one of the important components linking growth signals to the regulation of β-cell expansion. Downstream of AKT, tuberous sclerosis complex 1 and 2 (TSC1/2) and mechanistic target of rapamycin complex 1 (mTORC1) signaling have emerged as prime candidates in this process, because they integrate signals from growth factors and nutrients. Recent studies demonstrate the importance of mTORC1 signaling in β cells. This review will discuss recent advances in the understanding of how this pathway regulates β-cell mass and present data on the role of TSC1 in modulation of β-cell mass. Herein, we also demonstrate that deletion of Tsc1 in pancreatic β cells results in improved glucose tolerance, hyperinsulinemia and expansion of β-cell mass that persists with aging.

Original languageEnglish (US)
Pages (from-to)1892-1902
Number of pages11
JournalCell Cycle
Volume11
Issue number10
DOIs
StatePublished - May 15 2012

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Keywords

  • AKT
  • Cell cycle
  • Glucose homeostasis
  • Insulin
  • Islets and proliferation
  • S6K
  • TSC1
  • TSC2
  • mTORC1
  • β cells
  • β-cell signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Blandino-Rosano, M., Chen, A. Y., Scheys, J. O., Alejandro, E. U., Gould, A. P., Taranukha, T., Elghazi, L., Cras-Méneur, C., & Bernal-Mizrachi, E. (2012). MTORC1 signaling and regulation of pancreatic β-cell mass. Cell Cycle, 11(10), 1892-1902. https://doi.org/10.4161/cc.20036