ArticleHuman molecular genetics2015
Mice expressing reduced levels of hepatic glucose-6-phosphatase-α activity do not develop age-related insulin resistance or obesity.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Co-Administration of Trans-Resveratrol and L-Carnitine with a High-Fat and High-Carbohydrate Diet Modulates Liver Transcriptome in Obesity-Resistant DBA/2J Mice.International journal of molecular sciences · 2026Article
- Liver-Directed Gene Therapy Mitigates Early Nephropathy in Murine Glycogen Storage Disease Type Ia.Journal of inherited metabolic disease · 2025Article
- Base-editing corrects metabolic abnormalities in a humanized mouse model for glycogen storage disease type-Ia.Nature communications · 2024Article
- Diet-induced glial insulin resistance impairs the clearance of neuronal debris in Drosophila brain.PLoS biology · 2023Article
- Normalization of hepatic ChREBP activity does not protect against liver disease progression in a mouse model for Glycogen Storage Disease type Ia.Cancer & metabolism · 2023Article
- Glycogen storage disease type I: Genetic etiology, clinical manifestations, and conventional and gene therapies.Pediatric discovery · 2023Article
- Gene therapy and genome editing for type I glycogen storage diseases.Frontiers in molecular medicine · 2023Review
- Deciphering therapeutic options for neurodegenerative diseases: insights from SIRT1.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Modeling Phenotypic Heterogeneity of Glycogen Storage Disease Type 1a Liver Disease in Mice by Somatic CRISPR/CRISPR-associated protein 9-Mediated Gene Editing.Hepatology (Baltimore, Md.) · 2021Article
- Biomarkers in Glycogen Storage Diseases: An Update.International journal of molecular sciences · 2021Review
- Gene therapy using a novel G6PC-S298C variant enhances the long-term efficacy for treating glycogen storage disease type Ia.Biochemical and biophysical research communications · 2020Article
- Honokiol Improves Insulin Resistance, Hepatic Steatosis, and Inflammation in Type 2 DiabeticInternational journal of molecular sciences · 2019Article
- An evolutionary approach to optimizing glucose-6-phosphatase-α enzymatic activity for gene therapy of glycogen storage disease type Ia.Journal of inherited metabolic disease · 2019Article
- Gene therapy prevents hepatic tumor initiation in murine glycogen storage disease type Ia at the tumor-developing stage.Journal of inherited metabolic disease · 2019Article
- Liver-directed gene therapy for murine glycogen storage disease type Ib.Human molecular genetics · 2017Article
- Downregulation of pathways implicated in liver inflammation and tumorigenesis of glycogen storage disease type Ia mice receiving gene therapy.Human molecular genetics · 2017Article
- Glycogen storage disease type Ia mice with less than 2% of normal hepatic glucose-6-phosphatase-α activity restored are at risk of developing hepatic tumors.Molecular genetics and metabolism · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Glycogen storage disease type-Ia (GSD-Ia) is caused by a lack of glucose-6-phosphatase-α (G6Pase-α or G6PC) activity. We have shown that gene therapy mediated by a recombinant adeno-associated virus (rAAV) vector expressing human G6Pase-α normalizes blood glucose homeostasis in the global G6pc knockout (G6pc(-/-)) mice for 70-90 weeks. The treated G6pc(-/-) mice expressing 3-63% of normal hepatic G6Pase-α activity (AAV mice) produce endogenous hepatic glucose levels 61-68% of wild-type littermates, have a leaner phenotype and exhibit fasting blood insulin levels more typical of young adult mice. We now show that unlike wild-type mice, the lean AAV mice have increased caloric intake and do not develop age-related obesity or insulin resistance. Pathway analysis shows that signaling by hepatic carbohydrate response element binding protein that improves glucose tolerance and insulin signaling is activated in AAV mice. In addition, several longevity factors in the calorie restriction pathway, including the NADH shuttle systems, NAD(+) concentrations and the AMP-activated protein kinase/sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α pathway are upregulated in the livers of AAV mice. The finding that partial restoration of hepatic G6Pase-α activity in GSD-Ia mice not only attenuates the phenotype of hepatic G6Pase-α deficiency but also prevents the development of age-related obesity and insulin resistance seen in wild-type mice may suggest relevance of the G6Pase-α enzyme to obesity and diabetes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.