Lkb1 suppresses amino acid-driven gluconeogenesis in the liver
| العنوان: | Lkb1 suppresses amino acid-driven gluconeogenesis in the liver |
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| المؤلفون: | Just, Pierre-Alexandre, Charawi, Sara, Denis, Raphaël G. P., Savall, Mathilde, Traore, Massiré, Foretz, Marc, Bastu, Sultan, Magassa, Salimata, Senni, Nadia, Sohier, Pierre, Wursmer, Maud, Vasseur-Cognet, Mireille, Schmitt, Alain, Le Gall, Morgane, Leduc, Marjorie, Guillonneau, François, De Bandt, Jean-Pascal, Mayeux, Patrick, Romagnolo, Béatrice, Luquet, Serge, Bossard, Pascale, Perret, Christine |
| المساهمون: | Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Inserm U1016, Institut Cochin, Paris, France, 22 Rue Méchain, 75014 Paris, France, CNRS UMR8104, Paris, France, Université Paris Descartes, Sorbonne-Paris-Cité, Paris, France., Institut d'écologie et des sciences de l'environnement de Paris (IEES (UMR_7618 / UMR_D_242 / UMR_A_1392 / UM_113) ), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Sorbonne Université (SU)-Université de Paris (UP), Bossard, Pascale, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Prévention et traitement de la perte protéique musculaire en situation de résistance à l'anabolisme (PRETRRAM (URP_4466)), Université Paris Cité (UPCité), Institut d'écologie et des sciences de l'environnement de Paris (iEES Paris ), Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Paris (UP), Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) |
| المصدر: | Nature Communications Nature Communications, Nature Publishing Group, 2020, 11 (1), ⟨10.1038/s41467-020-19490-6⟩ Nature Communications, 2020, 11, pp.6127. ⟨10.1038/s41467-020-19490-6⟩ Nature Communications, Nature Publishing Group, 2020, 11, pp.6127. ⟨10.1038/s41467-020-19490-6⟩ Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020) |
| بيانات النشر: | Nature Publishing Group UK, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Proteomics, Sarcopenia, congenital, hereditary, and neonatal diseases and abnormalities, Cachexia, Physiology, Science, AMP-Activated Protein Kinases, Protein Serine-Threonine Kinases, Article, Mice, Animals, Amino Acids, Author Correction, skin and connective tissue diseases, Transaminases, Mice, Knockout, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Gluconeogenesis, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Fasting, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Glucose, Metabolism, Diabetes Mellitus, Type 2, Liver, Hyperglycemia, Hepatocytes, Female |
| الوصف: | Excessive glucose production by the liver is a key factor in the hyperglycemia observed in type 2 diabetes mellitus (T2DM). Here, we highlight a novel role of liver kinase B1 (Lkb1) in this regulation. We show that mice with a hepatocyte-specific deletion of Lkb1 have higher levels of hepatic amino acid catabolism, driving gluconeogenesis. This effect is observed during both fasting and the postprandial period, identifying Lkb1 as a critical suppressor of postprandial hepatic gluconeogenesis. Hepatic Lkb1 deletion is associated with major changes in whole-body metabolism, leading to a lower lean body mass and, in the longer term, sarcopenia and cachexia, as a consequence of the diversion of amino acids to liver metabolism at the expense of muscle. Using genetic, proteomic and pharmacological approaches, we identify the aminotransferases and specifically Agxt as effectors of the suppressor function of Lkb1 in amino acid-driven gluconeogenesis. Excessive glucose production by the liver contributes to poor blood glucose control in type 2 diabetes. Here the authors report that the liver kinase B1 (Lkb1) suppresses amino acid driven postprandial glucose production in the liver through the aminotransferase Agxt. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::5ac60abc100d7665d8dbed9a91e2be3cTest http://europepmc.org/articles/PMC7705018Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....5ac60abc100d7665d8dbed9a91e2be3c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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