The Role of Mammalian Target of Rapamycin (mTOR) in Insulin Signaling

Nutrients. 2017 Oct 27;9(11):1176. doi: 10.3390/nu9111176.

Abstract

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that controls a wide spectrum of cellular processes, including cell growth, differentiation, and metabolism. mTOR forms two distinct multiprotein complexes known as mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), which are characterized by the presence of raptor and rictor, respectively. mTOR controls insulin signaling by regulating several downstream components such as growth factor receptor-bound protein 10 (Grb10), insulin receptor substrate (IRS-1), F-box/WD repeat-containing protein 8 (Fbw8), and insulin like growth factor 1 receptor/insulin receptor (IGF-IR/IR). In addition, mTORC1 and mTORC2 regulate each other through a feedback loop to control cell growth. This review outlines the current understanding of mTOR regulation in insulin signaling in the context of whole body metabolism.

Keywords: insulin; mTOR complex1 (mTORC1); mTOR complex2 (mTORC2); mammalian target of rapamycin (mTOR); protein kinase B (PKB/Akt).

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Proliferation
  • F-Box Proteins / metabolism
  • GRB10 Adaptor Protein / metabolism
  • Humans
  • Insulin / metabolism*
  • Insulin Receptor Substrate Proteins / metabolism
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Mechanistic Target of Rapamycin Complex 2 / metabolism*
  • Rapamycin-Insensitive Companion of mTOR Protein / metabolism
  • Receptor, IGF Type 1 / metabolism
  • Receptor, Insulin / metabolism
  • Regulatory-Associated Protein of mTOR / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • F-Box Proteins
  • FBXW8 protein, human
  • IRS1 protein, human
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Rapamycin-Insensitive Companion of mTOR Protein
  • Regulatory-Associated Protein of mTOR
  • GRB10 Adaptor Protein
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Receptor, IGF Type 1
  • Receptor, Insulin
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2