What is the role of insulin signaling in mTOR?
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).
Does insulin trigger mTOR?
A postprandial increase of insulin and glucose acutely activates mTOR within metabolic tissues, in which mTOR plays an important role in glucose and lipid metabolism.
How does the mTOR pathway work?
Function. mTOR integrates the input from upstream pathways, including insulin, growth factors (such as IGF-1 and IGF-2), and amino acids. mTOR also senses cellular nutrient, oxygen, and energy levels. Rapamycin inhibits mTOR by associating with its intracellular receptor FKBP12.
How does mTOR regulate metabolism?
mTORC1 regulates hepatic lipid metabolism mainly through SREBP1, the master regulator of lipid synthesis. It is initially synthesized as an inactive precursor and localized in the ER. In response to the insulin signaling, SREBP1 is cleaved and transported to the nucleus to induce lipogenic gene expression.
Does glucose activate mTOR?
Mammalian target of rapamycin (mTOR) is a protein kinase that integrates signals from mitogens and the nutrients, glucose and amino acids, to regulate cellular growth and proliferation. Previous findings demonstrated that glucose robustly activates mTOR in an amino acid-dependent manner in rodent and human islets.
What happens if the mTOR pathway is inhibited?
The inhibition of mTOR blocks the binding of the accessory protein raptor (regulatory-associated protein of mTOR) to mTOR, but that is necessary for downstream phosphorylation of S6K1 and 4EBP1. As a consequence, S6K1 dephosphorylates, which reduces protein synthesis and decreases cell mortality and size.
What does mTOR pathway regulate?
The mTOR pathway is a central regulator of mammalian metabolism and physiology, with important roles in the function of tissues including liver, muscle, white and brown adipose tissue, and the brain, and is dysregulated in human diseases, such as diabetes, obesity, depression, and certain cancers.