{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Glucose‐6‐phosphatase catalytic subunit 1 (G6PC1) is a key enzyme expressed predominantly in the liver that catalyzes the hydrolysis of glucose‐6‐phosphate into free glucose and inorganic phosphate. This reaction represents the final and rate‐limiting step in both gluconeogenesis and glycogenolysis, processes that are essential for maintaining blood glucose homeostasis during fasting. In hepatocytes, the transcription of the G6PC1 gene is tightly regulated by several transcription factors and coactivators. For example, G6PC1 expression is critically dependent on the hepatocyte nuclear factor–4α (HNF4α), which, when coactivated by factors such as PGC-1α, drives the activation of gluconeogenic gene promoters during fasting states."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, nutrient- and hormone-sensitive regulators including SIRT1 further enhance gluconeogenic gene transcription—including that of G6PC1—by modulating key transcriptional regulators like FOXO1, thereby integrating signals of energy deprivation with the liver’s capacity to produce glucose."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Finally, downstream effects of insulin signaling also converge on the control of G6PC1 expression, as improved insulin responsiveness or targeted genetic modifications in hepatic signaling pathways result in reduced transcription of gluconeogenic genes, including G6PC1, which in turn contributes to improved glucose tolerance and lipid profiles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "James Rhee, Yusuke Inoue, J Cliff Yoon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of hepatic fasting response by PPARgamma coactivator-1alpha (PGC-1): requirement for hepatocyte nuclear factor 4alpha in gluconeogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0730870100"}], "href": "https://doi.org/10.1073/pnas.0730870100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12651943"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12651943"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yongzhan Nie, Derek M Erion, Zhenglong Yuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STAT3 inhibition of gluconeogenesis is downregulated by SirT1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1857"}], "href": "https://doi.org/10.1038/ncb1857"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19295512"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19295512"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mirela Delibegovic, Derek Zimmer, Caitlin Kauffman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Liver-specific deletion of protein-tyrosine phosphatase 1B (PTP1B) improves metabolic syndrome and attenuates diet-induced endoplasmic reticulum stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db08-0913"}], "href": "https://doi.org/10.2337/db08-0913"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19074988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19074988"}]}]}]}