{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:13:59Z","timestamp":1787944439213,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Maintaining constant blood glucose levels is essential for energizing glucose\u2010dependent tissues. During the fed state, insulin lowers elevated blood glucose, while in the fasted state, glucagon maintains blood glucose levels through hepatic stimulation of fatty acid oxidation, glycogenolysis, and gluconeogenesis (GNG). The liver plays a crucial role in these metabolic adaptations. Deregulation of GNG is a hallmark of type 2 diabetes mellitus (T2DM), driven by hepatic insulin resistance, elevated glucagon levels, and excess circulating free fatty acids. The glucose metabolism of 8\u2010 to 12\u2010week\u2010old WT and\n                    <jats:italic>Anxa6<\/jats:italic>\n                    knock\u2010out (\n                    <jats:italic>Anxa6<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) mice was analysed during regular feeding and fasting using indirect calorimetry, tolerance tests and biochemical analysis. Despite normal insulin\u2010sensitive control of glucose levels and effective glycogen mobilization,\n                    <jats:italic>Anxa6<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice display rapid hypoglycaemia during fasting. This metabolic disarrangement, in particular during the early stages of fasting is characterized by a low respiratory exchange ratio (RER) and increased lipid oxidation during the diurnal period, indicating a reliance on lipid oxidation due to hypoglycaemia. Elevated glucagon levels during fasting suggest deficiencies in GNG. Further analysis reveals that\n                    <jats:italic>Anxa6<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice are unable to utilize alanine for hepatic GNG, highlighting a specific impairment in the glucose\u2010alanine cycle in fasted\n                    <jats:italic>Anxa6<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, underscoring the critical role of ANXA6 in maintaining glucose homeostasis under metabolic stress. During fasting, slightly reduced expression levels of alanine aminotransferase 2 (\n                    <jats:italic>Gpt2<\/jats:italic>\n                    ) and lactate dehydrogenase (\n                    <jats:italic>Ldha2<\/jats:italic>\n                    ), enzymes converting alanine to pyruvate, and the hepatic alanine transporter SNAT4 might contribute to these observations in the\n                    <jats:italic>Anxa6<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. These findings identify that ANXA6 deficiency causes an inability to maintain glycolytic metabolism under fasting conditions due to impaired alanine\u2010dependent GNG.\n                  <\/jats:p>","DOI":"10.1002\/jcp.70084","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T18:00:13Z","timestamp":1755108013000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fasting\u2010Induced Hepatic Gluconeogenesis Is Compromised In\n                    <i>Anxa6<\/i>\n                    <sup>\n                      <i>\u2212\/\u2212<\/i>\n                    <\/sup>\n                    Mice"],"prefix":"10.1002","volume":"240","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9248-2275","authenticated-orcid":false,"given":"Anna","family":"Alvarez\u2010Guaita","sequence":"first","affiliation":[{"name":"Unit of Cell Biology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences University of Barcelona  Spain"},{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB\u2010IDIBAPS) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8200-6291","authenticated-orcid":false,"given":"Marc","family":"Bernaus\u2010Esqu\u00e9","sequence":"additional","affiliation":[{"name":"Unit of Cell Biology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences University of Barcelona  Spain"},{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB\u2010IDIBAPS) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Blanco\u2010Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Unit of Cell Biology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences University of Barcelona  Spain"},{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB\u2010IDIBAPS) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5002-4248","authenticated-orcid":false,"given":"Yangjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Unit of Cell Biology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences University of Barcelona  Spain"},{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB\u2010IDIBAPS) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7260-3869","authenticated-orcid":false,"given":"David","family":"Sebastian","sequence":"additional","affiliation":[{"name":"Departament de Bioqu\u00edmica i Fisiologia, Facultat de Farm\u00e0cia i Ci\u00e8ncies de l'Alimentaci\u00f3 Universitat de Barcelona  Spain"},{"name":"Institute of Biomedicine of the University of Barcelona (IBUB) Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"Meneses\u2010Salas","sequence":"additional","affiliation":[{"name":"Unit of Cell Biology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences University of Barcelona  Spain"},{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona\u2014Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (FRCB\u2010IDIBAPS) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai K. 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