ArticleMolecular and cellular biology2012
Transient neonatal diabetes mellitus gene Zac1 impairs insulin secretion in mice through Rasgrf1.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Impact of parental exercise on epigenetic modifications inherited by offspring: A systematic review.Physiological reports · 2019Pooled it
- PLAGL1 overexpression induces cytoplasmic DNA accumulation that triggers cGAS/STING activation.Journal of cellular and molecular medicine · 2024Article
- Importance of Both Imprinted Genes and Functional Heterogeneity in Pancreatic Beta Cells: Is There a Link?International journal of molecular sciences · 2021Review
- Imprinted Genes Impact Upon Beta Cell Function in the Current (and Potentially Next) Generation.Frontiers in endocrinology · 2021Review
- Identification of potential markers for type 2 diabetes mellitus via bioinformatics analysis.Molecular medicine reports · 2020Article
- Genome-wide identification of directed gene networks using large-scale population genomics data.Nature communications · 2018Article
- Chromosome 6q24-related diabetes mellitus.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2018Article
- Transcriptional regulatory dynamics drive coordinated metabolic and neural response to social challenge in mice.Genome research · 2017Article
- Single-cell transcriptomes identify human islet cell signatures and reveal cell-type-specific expression changes in type 2 diabetes.Genome research · 2017Article
- PLAGL1: an important player in diverse pathological processes.Journal of applied genetics · 2017Review
- Modeling Fetal Alcohol Spectrum Disorder: Validating an Ex Vivo Primary Hippocampal Cell Culture System.Alcoholism, clinical and experimental research · 2016Article
- Zac1 Regulates the Differentiation and Migration of Neocortical Neurons via Pac1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Role of ZAC1 in transient neonatal diabetes mellitus and glucose metabolism.World journal of biological chemistry · 2015Review
- Imprinted Zac1 in neural stem cells.World journal of stem cells · 2015Review
- Transcriptional profiling reveals functional links between RasGrf1 and Pttg1 in pancreatic beta cells.BMC genomics · 2014Article
- Degree of methylation of ZAC1 (PLAGL1) is associated with prenatal and post-natal growth in healthy infants of the EDEN mother child cohort.Epigenetics · 2014Article
- Zac1 regulates cell cycle arrest in neuronal progenitors via Tcf4.Molecular and cellular biology · 2014Article
- Microarray analysis of novel candidate genes responsible for glucose-stimulated insulin secretion in mouse pancreatic β cell line MIN6.PloS one · 2013Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The biallelic expression of the imprinted gene ZAC1/PLAGL1 underlies ≈ 60% of all cases of transient neonatal diabetes mellitus (TNDM) that present with low perinatal insulin secretion. Molecular targets of ZAC1 misexpression in pancreatic β cells are unknown. Here, we identified the guanine nucleotide exchange factor Rasgrf1 as a direct Zac1/Plagl1 target gene in murine β cells. Doubling Zac1 expression reduced Rasgrf1 expression, the stimulus-induced activation of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways, and, ultimately, insulin secretion. Normalizing Rasgrf1 expression reversed this phenotype. Moreover, the transplantation of Zac1-overexpressing β cells failed to reinstate euglycemia in experimental diabetic mice. In contrast, Zac1 expression did not interfere with the signaling of the glucagon-like peptide 1 receptor (GLP-1R), and the GLP-1 analog liraglutide improved hyperglycemia in transplanted experimental diabetic mice. This study unravels a mechanism contributing to insufficient perinatal insulin secretion in TNDM and raises new prospects for therapy.
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