The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin

By R. Shaw, Katja A. Lamia, Debbie S. Vasquez, Seung-Hoi Koo, N. Bardeesy, R. DePinho, M. Montminy, Lewis C. Cantley. Science, 2005

2,021 citations recorded by the source corpus.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e8dbfd9f625841a52c4e3714b1a577c2b16c94da

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Citations in the corpus

Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. (2009, background): “In hepatocytes, this results in inhibition of gluconeogenesis, and this is the principal mediator of the glucose- and insulin-lowering effects of metformin.(37) Under low-energy and other stress conditions, AMPK phosphorylates a number of targets to inhibit cellular growth and proliferation, includi”
Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. (2006, background): “As the metabolic actions of metformin require AMP kinase (3), we hypothesized that the antiproliferative effects of metformin involve the same pathway.”
Cellular and molecular mechanisms of metformin: an overview. (2012, background): “Metformin most likely does not directly activate either LKB1 or AMPK as the drug does not influence the phosphorylation of AMPK by LKB1 in cell-free assay [21].”
Energy Metabolism in the Liver (2014, positive): “The LKB1/AMP pathway suppresses HGP. Liver-speciﬁc deletion of LKB1 increases hepatic gluconeo-genesis and blood glucose levels (242), and genetic deletion of AMPK α 2 in the liver also increases hepatic gluconeogenesis and glucose intolerance (5).”
Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism. (2008, background): “Metformin, widely prescribed for over 40 yr in Europe, enhances AMP kinase activity via an unknown mechanism that requires the upstream kinase LKB1 (151).”
Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress (2010, background): “Activation of AMPK and subsequent inhibition of mTORC1 occurs in response to these drugs, but the contribution of this signaling pathway to the antidiabetic effects of the drugs remains unclear (Foretz et al., 2010; Shaw et al., 2005).”
AMPK phosphorylation of raptor mediates a metabolic checkpoint. (2008, background): “We have previously shown that metformin rapidly activates AMPK in murine liver in manner completely dependent on LKB1 (Shaw et al., 2005).”
Metformin, Independent of AMPK, Inhibits mTORC1 In a Rag GTPase-Dependent Manner (2010, background): “These effects are attributed to activation of AMPK, and, in the case of hepatic gluconeogenesis, recent studies in LKB1 / -deficient mice support such a model (Shaw et al., 2005).”