ArticleHuman molecular genetics2023
Molecular mechanism underlying impaired hepatic autophagy in glycogen storage disease type Ib.
Article in Human molecular genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- Fabry disease cardiomyopathy: A state-of-the-art review.Progress in cardiovascular diseasesPooled it
- A newborn with glycogen storage disease type Ib presenting with hypoglycemia and evidence of mitochondrial dysfunction.Molecular genetics and metabolism reports · 2026Article
- Hepatocyte-specific Cas9-mediated editing of G6pc and Slc37a4 elicits comparable biochemical and regulatory responses between glycogen storage disease (GSD) type Ia and Ib mice.Molecular metabolism · 2026Article
- The glucose-6-phosphatase system in cancer: from endoplasmic reticulum glucose-6-phosphate flux to stemness, immune escape, and therapeutic vulnerability.Frontiers in oncology · 2026Review
- Zebrafish navigating the metabolic maze: insights into human disease - assets, challenges and future implications.Journal of diabetes and metabolic disorders · 2025Review
- Hepatocellular adenoma update: diagnosis, molecular classification, and clinical course.The British journal of radiology · 2024Review
- A novelMolecular genetics and metabolism reports · 2024Article
- Bufei Yishen formula protects the airway epithelial barrier and ameliorates COPD by enhancing autophagy through the Sirt1/AMPK/Foxo3 signaling pathway.Chinese medicine · 2024Article
- Ethanol Extract ofMolecules (Basel, Switzerland) · 2023Article
- Gene therapy and genome editing for type I glycogen storage diseases.Frontiers in molecular medicine · 2023Review
- Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders.Frontiers in endocrinology · 2023Review
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Type Ib glycogen storage disease (GSD-Ib) is caused by a deficiency in the glucose-6-phosphate (G6P) transporter (G6PT) that translocates G6P from the cytoplasm into the endoplasmic reticulum lumen, where the intraluminal G6P is hydrolyzed to glucose by glucose-6-phosphatase-α (G6Pase-α). Clinically, GSD-Ib patients manifest a metabolic phenotype of impaired blood glucose homeostasis and a long-term risk of hepatocellular adenoma/carcinoma (HCA/HCC). Studies have shown that autophagy deficiency contributes to hepatocarcinogenesis. In this study, we show that G6PT deficiency leads to impaired hepatic autophagy evident from attenuated expression of many components of the autophagy network, decreased autophagosome formation and reduced autophagy flux. The G6PT-deficient liver displayed impaired sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK) signaling, along with reduced expression of SIRT1, forkhead boxO3a (FoxO3a), liver kinase B-1 (LKB1) and the active p-AMPK. Importantly, we show that overexpression of either SIRT1 or LKB1 in G6PT-deficient liver restored autophagy and SIRT1/FoxO3a and LKB1/AMPK signaling. The hepatosteatosis in G6PT-deficient liver decreased SIRT1 expression. LKB1 overexpression reduced hepatic triglyceride levels, providing a potential link between LKB1/AMPK signaling upregulation and the increase in SIRT1 expression. In conclusion, downregulation of SIRT1/FoxO3a and LKB1/AMPK signaling underlies impaired hepatic autophagy which may contribute to HCA/HCC development in GSD-Ib. Understanding this mechanism may guide future therapies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.