SynthesisDiabetologia2012
A common variant upstream of the PAX6 gene influences islet function in man.
Synthesis in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- scParser: sparse representation learning for scalable single-cell RNA sequencing data analysis.Genome biology · 2024Article
- A critical review on therapeutic approaches of CRISPR-Cas9 in diabetes mellitus.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Transcriptional Signatures and Network-Based Approaches Identified Master Regulators Transcription Factors Involved in Experimental Periodontitis Pathogenesis.International journal of molecular sciences · 2023Article
- Autoregulation of Pax6 in neuronal cells is mediated by Pax6(5a), Pax6(ΔPD), SPARC, and p53.Molecular biology reports · 2022Article
- Transient Hyperinsulinemic Hypoglycemia Linked toMedicina (Kaunas, Lithuania) · 2021Article
- Lack of association between PAX6/SOSTDC1/FAM20B gene polymorphisms and mesiodens.BMC oral health · 2019Article
- Protecting Pax6 3' UTR from MicroRNA-7 Partially Restores PAX6 in Islets from an Aniridia Mouse Model.Molecular therapy. Nucleic acids · 2018Article
- Article
- The transcription factorThe Journal of biological chemistry · 2017Article
- Diabetes: Controlling the identity of the adult pancreatic β cell.Nature reviews. Endocrinology · 2017Article
- PAX6 maintains β cell identity by repressing genes of alternative islet cell types.The Journal of clinical investigation · 2017Article
- PCSK1 Variants and Human Obesity.Progress in molecular biology and translational science · 2016Review
- Pax6 influences expression patterns of genes involved in neuro- degeneration.Annals of neurosciences · 2015Article
- A novel 11p13 microdeletion encompassing PAX6 in a Chinese Han family with aniridia, ptosis and mental retardation.Molecular cytogenetics · 2015Article
- A stress response pathway in mice upregulates somatostatin level and transcription in pancreatic delta cells through Gs and β-arrestin 1.Diabetologia · 2014Article
- Revealing transcription factors during human pancreatic β cell development.Trends in endocrinology and metabolism: TEM · 2014Review
- The developmental regulator Pax6 is essential for maintenance of islet cell function in the adult mouse pancreas.PloS one · 2013Article
- γ-Aminobutyric acid (GABA) signalling in human pancreatic islets is altered in type 2 diabetes.Diabetologia · 2012Article
- Interaction between Pax6 and its novel mutant in Bufo raddei Strauch.Molecular vision · 2011Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisImpaired glucose tolerance and impaired insulin secretion have been reported in families with PAX6 mutations and it is suggested that they result from defective proinsulin processing due to lack of prohormone convertase 1/3, encoded by PCSK1. We investigated whether a common PAX6 variant would mimic these findings and explored in detail its effect on islet function in man.
methodsA PAX6 candidate single nucleotide polymorphism (rs685428) was associated with fasting insulin levels in the Diabetes Genetics Initiative genome-wide association study. We explored its potential association with glucose tolerance and insulin processing and secretion in three Scandinavian cohorts (N = 8,897 individuals). In addition, insulin secretion and the expression of PAX6 and transcriptional target genes were studied in human pancreatic islets.
resultsrs685428 G allele carriers had lower islet mRNA expression of PAX6 (p = 0.01) and PCSK1 (p = 0.001) than AA homozygotes. The G allele was associated with increased fasting insulin (p (replication) = 0.02, p (all) = 0.0008) and HOMA-insulin resistance (p (replication) = 0.02, p (all) = 0.001) as well as a lower fasting proinsulin/insulin ratio (p (all) = 0.008) and lower fasting glucagon (p = 0.04) and gastric inhibitory peptide (GIP) (p = 0.05) concentrations. Arginine-stimulated (p = 0.02) insulin secretion was reduced in vivo, which was further reflected by a reduction of glucose- and potassium-stimulated insulin secretion (p = 0.002 and p = 0.04, respectively) in human islets in vitro. CONCLUSIONS/
interpretationA common variant in PAX6 is associated with reduced PAX6 and PCSK1 expression in human islets and reduced insulin response, as well as decreased glucagon and GIP concentrations and decreased insulin sensitivity. These findings emphasise the central role of PAX6 in the regulation of islet function and glucose metabolism in man.
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