ArticleJournal of molecular endocrinology2020
Pancreatic islet beta cell-specific deletion of G6pc2 reduces fasting blood glucose.
Article in Journal of molecular endocrinology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.Nature genetics · 2023Pooled it
- Generation of human islet cell type-specific identity genesets.Nature communications · 2022Pooled it
- Crosstalk between the aryl hydrocarbon receptor and hypoxia-inducible factor 1α pathways in human islet models.Islets · 2025Article
- From Human to Mouse and Back Again: Genetic and Genomic Ta(i)les of Islet Dysfunction in Type 2 Diabetes.Annual review of genetics · 2025Review
- Review
- Identifying patterns differing between high-dimensional datasets with generalized contrastive PCA.PLoS computational biology · 2025Article
- G6PC2 controls glucagon secretion by defining the set point for glucose in pancreatic α cells.Science translational medicine · 2025Article
- Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice.Nature communications · 2024Article
- Multiple promoter and enhancer differences likely contribute to augmented G6PC2 expression in human versus mouse pancreatic islet alpha cells.Journal of molecular endocrinology · 2024Article
- Association between MAPK and PI3K/Akt signaling pathway-related gene polymorphisms and migraine.Molecular genetics & genomic medicine · 2024Article
- Article
- Biochemical and metabolic characterization of a G6PC2 inhibitor.Biochimie · 2024Article
- Identification of structural motifs critical for human G6PC2 function informed by sequence analysis and an AlphaFold2-predicted model.Bioscience reports · 2024Article
- G6PC1 and G6PC2 influence G6P flux but not HSD11B1 activity.Journal of molecular endocrinology · 2023Article
- Article
- Haplotypes of the genes (GCK and G6PC2) underlying the glucose/glucose-6-phosphate cycle are associated with pancreatic beta cell glucose sensitivity in patients with newly diagnosed type 2 diabetes from the VNDS study (VNDS 11).Journal of endocrinological investigation · 2021Article
- Mechanisms controlling pancreatic islet cell function in insulin secretion.Nature reviews. Molecular cell biology · 2021Review
- Glucose metabolism-related gene polymorphisms as the risk predictors of type 2 diabetes.Diabetology & metabolic syndrome · 2020Review
- G6PC2 confers protection against hypoglycemia upon ketogenic diet feeding and prolonged fasting.Molecular metabolism · 2020Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
The G6PC1, G6PC2 and G6PC3 genes encode distinct glucose-6-phosphatase catalytic subunit (G6PC) isoforms. In mice, germline deletion of G6pc2 lowers fasting blood glucose (FBG) without affecting fasting plasma insulin (FPI) while, in isolated islets, glucose-6-phosphatase activity and glucose cycling are abolished and glucose-stimulated insulin secretion (GSIS) is enhanced at submaximal but not high glucose. These observations are all consistent with a model in which G6PC2 regulates the sensitivity of GSIS to glucose by opposing the action of glucokinase. G6PC2 is highly expressed in human and mouse islet beta cells however, various studies have shown trace G6PC2 expression in multiple tissues raising the possibility that G6PC2 also affects FBG through non-islet cell actions. Using real-time PCR we show here that expression of G6pc1 and/or G6pc3 are much greater than G6pc2 in peripheral tissues, whereas G6pc2 expression is much higher than G6pc3 in both pancreas and islets with G6pc1 expression not detected. In adult mice, beta cell-specific deletion of G6pc2 was sufficient to reduce FBG without changing FPI. In addition, electronic health record-derived phenotype analyses showed no association between G6PC2 expression and phenotypes clearly unrelated to islet function in humans. Finally, we show that germline G6pc2 deletion enhances glycolysis in mouse islets and that glucose cycling can also be detected in human islets. These observations are all consistent with a mechanism by which G6PC2 action in islets is sufficient to regulate the sensitivity of GSIS to glucose and hence influence FBG without affecting FPI.
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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.