The role of mTOR in the adaptation and failure of β-cells in type 2 diabetes

Gil Leibowitz*, E. Cerasi, M. Ketzinel-Gilad

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Mammalian target of rapamycin (mTOR) is an important nutrient sensor that plays a critical role in cellular metabolism, growth, proliferation and apoptosis and in the cellular response to oxidative stress. In addition, mTOR - raptor complex, also called mammalian target of rapamycin complex 1 (mTORC1), generates an inhibitory feedback loop on insulin receptor substrate proteins. It was suggested that nutrient overload leads to insulin/insulin-like growth factor 1 resistance in peripheral insulin-responsive tissues and in the β-cells through sustained activation of mTORC1. In this review, we summarize the literature on the regulation and function of mTOR, its role in the organism's response to nutrients and its potential impact on lifespan, insulin resistance and the metabolic adaptation to hyperglycaemia in type 2 diabetes. We also propose a hypothesis based on data in the literature as well as data generated in our laboratory, which assigns a central positive role to mTOR in the maintenance of β-cell function and mass in the diabetic environment.

Original languageAmerican English
Pages (from-to)157-169
Number of pages13
JournalDiabetes, Obesity and Metabolism
Volume10
Issue numberSUPPL. 4
DOIs
StatePublished - 2008
Externally publishedYes

Keywords

  • Insulin secretion
  • Lifespan
  • Metabolism
  • Rapamycin
  • mTOR
  • β-cell

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