Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis

By Shijie Li, Michael S. Brown, J. Goldstein. Proceedings of the National Academy of Sciences of the United States of America, 2010

733 citations recorded by the source corpus.

Subfields: Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/b34dcb3971cb93bfed34f18d52fc503d4504fa23

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Citations in the corpus

Mechanisms of Hepatic Triglyceride Accumulation in Nonalcoholic Fatty Liver Disease (2013, unknown): “Within the insulin signaling pathway, the mammalian target of rapamycin complex 1 (mTORC1) and insulin induced gene 2A (INSIG2A) are required for stimulation of lipogenesis [39, 40], but apparently not for inhibition of gluconeogenesis [39], which is regulated by the transcription factor forkhead bo”
The PI3K/AKT pathway in obesity and type 2 diabetes (2018, background): “In the feeding state, SREBP-1c is regulated by four pathways: activated AKT stimulates liver X receptor (LXR), which is require for SREBP-1c transcription [64]; activated AKT stimulates mTORC1 to activate SREBP-1c transcription, and mTORC1 also inhibits Lipin-1, which decreases the half-life of nucl”
Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP‐1c (2010, background): “A similar selective effect of rapamycin was found in livers of rats and mice submitted to a fasting-refeeding protocol [27].”
Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways (2011, methodology): “Furthermore, a recent study has shown that the ability of insulin to stimulate SREBP1c in rat hepatocytes is sensitive to the mTORC1-specific inhibitor rapamycin (Li et al., 2010).”
mTOR signaling in growth control and disease (2012, unknown): “…inhibition reduces SREBP1 and 2 expression, impairs their processing, and markedly lowers the expression of lipogenic genes (Düvel et al., 2010; Li et al., 2010; Porstmann et al., 2008; Wang et al., 2011). mTORC1 appears to regulate SREBP function through several mechanisms, including, at…”
Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2 (2012, background): “Thus, though AKT signalling to mTORC1 is diminished in diabetes, the over-supply of nutrients in obesity is hypothesised to promote mTORC1/S6K phosphorylation of IRS and other targets, aggravating insulin resistance (reviewed in [109, 110]).”
Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease. (2019, background): “Studies conducted in primary hepatocytes and in rodent models of obesity and diabetes support the notion of selective pathway-specific insulin resistance in the liver (31-34).”
Regulation of mTORC1 and its impact on gene expression at a glance (2013, background): “Blocking of mTOR signaling reduces the mRNA and protein levels of SREBPs in several experimental models (Li et al., 2010; Li et al., 2011; Owen et al., 2012; Wang et al., 2011; Yecies et al., 2011).”
The interaction of hepatic lipid and glucose metabolism in liver diseases. (2012, background): “Interestingly, rapamycin treatment also downregulates SREBP-1c in primary hepatocytes, which suggests an effect of rapamycin, independent of mTOR, on the activity of forkhead box protein O (FoxO) [40].”
Energy Metabolism in the Liver (2014, unknown): “genesis and gluconeogenesis are mediated by two distinct pathways downstream of Akt (144).”
Insulin Resistance: From Mechanisms to Therapeutic Strategies (2021, background): “This process is called hepatic glucose production (HGP), and involves the breakdown of hepatic glycogen (glycogenolysis) and de novo synthesis of glucose (gluconeogenesis) using fatty acids and glycerol derived from adipose tissues [3].”