Role of the mammalian target of rapamycin (mTOR) complexes in pancreatic β-cell mass regulation

Vitam Horm. 2014;95:425-69. doi: 10.1016/B978-0-12-800174-5.00017-X.

Abstract

Exquisite regulation of insulin secretion by pancreatic β-cells is essential to maintain metabolic homeostasis. β-Cell mass must be accordingly adapted to metabolic needs and can be largely modified under different situations. The mammalian target of rapamycin (mTOR) complexes has been consistently identified as key modulators of β-cell mass. mTOR can be found into two different complexes, mTORC1 and mTORC2. Under systemic insulin resistance, mTORC1/mTORC2 signaling in β-cells is needed to increase β-cell mass and insulin secretion. However, type 2 diabetes arises when these compensatory mechanisms fail, being the role of mTOR complexes still obscure in β-cell failure. In this chapter, we introduce the protein composition and regulation of mTOR complexes and their role in pancreatic β-cells. Furthermore, we describe their main signaling effectors through the review of numerous animal models, which indicate the essential role of mTORC1/mTORC2 in pancreatic β-cell mass regulation.

Keywords: Autophagy; ER stress; Pancreatic β-cell mass; TSC2; mTORC1; mTORC2.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / physiopathology
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • Models, Biological*
  • Multiprotein Complexes / metabolism*
  • Pancreas / cytology
  • Pancreas / pathology
  • Pancreas / physiology
  • Pancreas / physiopathology
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Insulin
  • Multiprotein Complexes
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2