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Cell Metab. 2018 Feb 6;27(2):314-331. doi: 10.1016/j.cmet.2017.11.004. Epub 2017 Dec 21.

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

Author information

1
University of Bremen, Centre for Biomolecular Interactions Bremen, Bremen 28359, Germany. Electronic address: ardestani.amin@gmail.com.
2
University of Bremen, Centre for Biomolecular Interactions Bremen, Bremen 28359, Germany.
3
Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Division of Metabolism and Disease, Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe 654-0142, Japan.
4
Endocrinology and Metabolism Service and the Hadassah Diabetes Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
5
University of Bremen, Centre for Biomolecular Interactions Bremen, Bremen 28359, Germany. Electronic address: kmaedler@uni-bremen.de.

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.

KEYWORDS:

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

PMID:
29275961
DOI:
10.1016/j.cmet.2017.11.004

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