Abstract
The mechanistic target of rapamycin (mTOR) signaling pathway is an evolutionary conserved pathway that senses signals from nutrients and growth factors to regulate cell growth, metabolism and survival. mTOR acts in two biochemically and functionally distinct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), which differ in terms of regulatory mechanisms, substrate specificity and functional outputs. While mTORC1 signaling has been extensively studied in islet/β-cell biology, recent findings demonstrate a distinct role for mTORC2 in the regulation of pancreatic β-cell function and mass. mTORC2, a key component of the growth factor receptor signaling, is declined in β cells under diabetogenic conditions and in pancreatic islets from patients with type 2 diabetes. β cell-selective mTORC2 inactivation leads to glucose intolerance and acceleration of diabetes as a result of reduced β-cell mass, proliferation and impaired glucose-stimulated insulin secretion. Thereby, many mTORC2 targets, such as AKT, PKC, FOXO1, MST1 and cell cycle regulators, play an important role in β-cell survival and function. This indicates mTORC2 as important pathway for the maintenance of β-cell homeostasis, particularly to sustain proper β-cell compensator...Continue Reading
Citations
Dec 7, 2018·The Journal of Biological Chemistry·Kwan Yi ChuTrevor J Biden
Dec 5, 2018·Oxidative Medicine and Cellular Longevity·Yongting LuoWei Cui
Sep 10, 2020·Genes·Wenxiang Fu, Michael N Hall
Jul 3, 2020·Scientific Reports·S SeddaG Monteleone
Sep 12, 2019·Platelets·Mauro TortiGianni Francesco Guidetti
Jul 20, 2019·BMC Biology·Pundrik Jaiswal, Alan R Kimmel
Jul 8, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lien D NguyenBarbara E Ehrlich
Jan 15, 2021·Developmental and Comparative Immunology·Zhimeng LvMing Guo
Jan 19, 2021·Journal of Diabetes Research·Nicholas EschEmilyn U Alejandro
Mar 4, 2021·Stem Cells Translational Medicine·Manasa P SrikanthRicardo A Feldman
Apr 4, 2021·Cells·Nan WangYufei Gao
May 1, 2021·International Journal of Molecular Sciences·Jan ŠrámekJan Kovář
Aug 5, 2021·Cell Reports·Blaz LupseAmin Ardestani
Sep 27, 2020·Scientific Reports·Ghada A Soliman, C Mary Schooling