mTORC1 Signaling: A Double-Edged Sword in Diabetic β Cells

Amin Ardestani*, Blaz Lupse, Yoshiaki Kido, Gil Leibowitz, Kathrin Maedler

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

127 Scopus citations

Abstract

The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of metabolic and nutrient cues that integrates environmental inputs into downstream signaling pathways to control cellular metabolism, growth, and survival. While numerous in vitro and in vivo studies reported the positive functions of mTORC1 in the regulation of β cell survival and proliferation under physiological conditions, more recent work demonstrates the opposite in the long term; this is exemplified by the constitutive inappropriate hyper-activation of mTORC1 in diabetic islets or β cells under conditions of increased β cell stress and metabolic demands. These recent findings uncover mTORC1‘s importance as an emerging significant player in the development and progression of β cell failure in type 2 diabetes and suggest that mTORC1 may act as a “double edge sword” in the regulation of β cell mass and function in response to metabolic stress such as nutrient overload and insulin resistance. In this review, Ardestani et al. present the positive and negative effects of mTORC1 signaling in the β cell and discuss the implications for metabolic disease therapies. While essential for β cell development, function, and survival, mTORC1’s hyperactivation under constant metabolic stress contributes to β cell failure.

Original languageAmerican English
Pages (from-to)314-331
Number of pages18
JournalCell Metabolism
Volume27
Issue number2
DOIs
StatePublished - 6 Feb 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Elsevier Inc.

Keywords

  • apoptosis
  • cell
  • diabetes
  • insulin
  • mTOR
  • mTORC1
  • mTORC2
  • pancreas
  • β

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