ArticleMolecular and cellular biology2009
Pax6 regulates the proglucagon processing enzyme PC2 and its chaperone 7B2.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- A common variant upstream of the PAX6 gene influences islet function in man.Diabetologia · 2012Pooled it
- Type 2 diabetes is associated with impaired jejunal enteroendocrine GLP-1 cell lineage in human obesity.International journal of obesity (2005) · 2021Trial
- Early blood DNA methylation patterns associated with glycemic progression in a prospective Indian cohort.Clinical epigenetics · 2026Article
- Review
- Chronic Exposure to Palmitate Impairs Insulin Signaling in an Intestinal L-cell Line: A Possible Shift from GLP-1 to Glucagon Production.International journal of molecular sciences · 2018Article
- Glucose-dependent downregulation of glucagon gene expression mediated by selective interactions between ALX3 and PAX6 in mouse alpha cells.Diabetologia · 2016Article
- Pax6 Inactivation in the Adult Pancreas Reveals Ghrelin as Endocrine Cell Maturation Marker.PloS one · 2015Article
- The developmental regulator Pax6 is essential for maintenance of islet cell function in the adult mouse pancreas.PloS one · 2013Article
- Microarray analysis of novel candidate genes responsible for glucose-stimulated insulin secretion in mouse pancreatic β cell line MIN6.PloS one · 2013Article
- Pax6 is crucial for β-cell function, insulin biosynthesis, and glucose-induced insulin secretion.Molecular endocrinology (Baltimore, Md.) · 2012Article
- Article
- Isosteviol has beneficial effects on palmitate-induced α-cell dysfunction and gene expression.PloS one · 2012Article
- Pax6 directly down-regulates Pcsk1n expression thereby regulating PC1/3 dependent proinsulin processing.PloS one · 2012Article
- Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell differentiation to a somatostatin/ghrelin co-expressing cell lineage.BMC developmental biology · 2011Article
- Pax6 controls the expression of critical genes involved in pancreatic {alpha} cell differentiation and function.The Journal of biological chemistry · 2010Article
- Relative roles of the different Pax6 domains for pancreatic alpha cell development.BMC developmental biology · 2010Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pax6 is important in the development of the pancreas and was previously shown to regulate pancreatic endocrine differentiation, as well as the insulin, glucagon, and somatostatin genes. Prohormone convertase 2 (PC2) is the main processing enzyme in pancreatic alpha cells, where it processes proglucagon to produce glucagon under the spatial and temporal control of 7B2, which functions as a molecular chaperone. To investigate the role of Pax6 in glucagon biosynthesis, we studied potential target genes in InR1G9 alpha cells transfected with Pax6 small interfering RNA and in InR1G9 clones expressing a dominant-negative form of Pax6. We now report that Pax6 controls the expression of the PC2 and 7B2 genes. By binding and transactivation studies, we found that Pax6 indirectly regulates PC2 gene transcription through cMaf and Beta2/NeuroD1 while it activates the 7B2 gene both directly and indirectly through the same transcription factors, cMaf and Beta2/NeuroD1. We conclude that Pax6 is critical for glucagon biosynthesis and processing by directly and indirectly activating the glucagon gene through cMaf and Beta2/NeuroD1, as well as the PC2 and 7B2 genes.
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