Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
Diabetologia
Published in: Diabetologia 3/2009

01-03-2009 | Commentary

Not for the eyes only: PAX6 and glucose metabolism

Author: M. Laakso

Published in: Diabetologia | Issue 3/2009

Login to get access

Excerpt

Paired box 6 (PAX6) is a member of the PAX multigene family of transcription factors: this family regulates embryonic differentiation. Nine unlinked PAX genes dispersed throughout the genome encode proteins that each include a 128-amino-acid sequence-specific highly conserved DNA-binding domain, the Paired box, which can regulate the expression of other genes [1]. PAX6 also contains another common DNA-binding element: the homeobox that encodes a 60-amino-acid homeodomain responsible for target sequence recognition [2]. The paired domain and homeodomain interact cooperatively to recognise multiple DNA binding sites [3]. …
Literature
1.
Mark M, Rijli FM, Chambon P (1997) Homeobox genes in embryogenesis and pathogenesis. Ped Res 42:421–429CrossRef
2.
Glaser T, Walton DS, Maas RL (1992) Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene. Nat Genet 2:232–239PubMedCrossRef
3.
Jun S, Desplan C (1996) Cooperative interactions between paired domain and homeodomain. Development 122:2639–2650PubMed
4.
5.
Marsich E, Vetere A, Di Piazza M, Tell G, Paoletti S (2003) The PAX6 gene is activated by the basic helix–loop–helix transcription factor NeuroD/BETA2. Biohem J 376:707–715
6.
Sander M, Neubuser A, Kalamaras J, Ee HC, Martin GR, German MS (1997) Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development. Genes Dev 11:1662–1673PubMedCrossRef
7.
Glaser T, Jepeal L, Edwards JG, Young SR, Favor J, Maas RL (1994) PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects. Nat Genet 7:463–471PubMedCrossRef
8.
St-Onge L, Sosa-Pineda B, Chowdhury K, Mansouri A, Gruss P (1997) Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas. Nature 387:406–409PubMedCrossRef
9.
Sisodiya SM, Free SL, Wlliamson KA et al (2001) PAX6 haploinsufficiency causes cerebral malformation and olfactory dysfunction in humans. Nat Genet 28:214–216PubMedCrossRef
10.
Yasuda T, Kajimoto Y, Fujitani Y et al (2002) PAX6 mutation as a genetic factor common to aniridia and glucose intolerance. Diabetes 51:224–230PubMedCrossRef
11.
Nishi M, Sasahara M, Shono T et al (2005) A case of novel de novo paired box gene 6 (PAX6) mutation with early-onset diabetes mellitus and aniridia. Diabet Med 22:641–644PubMedCrossRef
12.
Wen JH, Chen YY, Song SJ et al (2008) Paired box 6 (PAX6) regulates glucose metabolism via proinsulin processing mediated by prohormone convertase 1/3 (PC1/3). Diabetologia. doi: 10.​1007/​s00125-008-1210-x
13.
Ashery-Padan R, Zhou X, Marquardt T et al (2004) Conditional inactivation of Pax6 in the pancreas causes early onset of diabetes. Dev Biol 269:479–488PubMedCrossRef
14.
Frayling TM (2007) Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nat Rev Genet 8:657–662PubMedCrossRef
15.
Lyttle BM, Li J, Krishnamurthy M, Fellows F et al (2008) Transcription factor expression in the developing human fetal endocrine pancreas. Diabetologia 51:1169–1180PubMedCrossRef
16.
Wang J, Elghazi L, Parker SE et al (2004) The concerted activities of Pax4 and Nkx2.2 are essential to initiate pancreatic beta-cell differentiation. Dev Biol 266:178–189PubMedCrossRef
17.
Sosa-Pineda B (2004) The gene Pax4 is an essential regulator of pancreatic beta-cell development. Mol Cells 18:289–294PubMed
18.
Hamasaki A, Yamada Y, Kurose T et al (2007) Adult pancreatic islets require different pax6 gene dosage. Biochem Biophys Res Commun 353:40–46PubMedCrossRef
19.
Schonhoff SE, Giel-Moloney M, Leiter AB (2004) Minireview: development and differentiation of gut endocrine cells. Endocrinology 145:2639–2644PubMedCrossRef
20.
Krätzner R, Frölich F, Lepler K et al (2008) A peroxisome proliferator-activated receptor gamma-retinoid X receptor heterodimer physically interacts with the transcriptional activator PAX6 to inhibit glucagons gene transcription. Mol Pharmacol 73:509–517PubMedCrossRef
21.
Hill ME, Asa SL, Drucker DJ (1999) Essential requirement for Pax6 in control of enteroendocrine proglucagon gene transcription. Mol Endocrinol 13:1474–1486PubMedCrossRef
22.
Larsson LI, St-Onge L, Hougaard DM, Sosa-Pineda B, Gruss P (2008) Pax4 and 6 regulate gastrointestinal endocrine cell development. Mech Dev 79:153–159CrossRef
23.
Cao X, Flock G, Choi C, Irwin DM, Drucker DJ (2003) Aberrant regulation of human intestinal proglucagon gene expression in the NCI-H716 cell line. Endocrinology 144:2025–2033PubMedCrossRef
Metadata
Title
Not for the eyes only: PAX6 and glucose metabolism
Author
M. Laakso
Publication date
01-03-2009
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 3/2009
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-008-1251-1

Other articles of this Issue 3/2009

Diabetologia 3/2009 Go to the issue

Article

Complexity of factors related to outcome of neuropathic and neuroischaemic/ischaemic diabetic foot ulcers: a cohort study

Article

Cluster analysis of rat pancreatic islet gene mRNA levels after culture in low-, intermediate- and high-glucose concentrations

Article

Continuous relationships between non-diabetic hyperglycaemia and both cardiovascular disease and all-cause mortality: the Australian Diabetes, Obesity, and Lifestyle (AusDiab) study

Article

Ghrelin-producing epsilon cells in the developing and adult human pancreas

Erratum

Apolipoproteins, cardiovascular risk and statin response in type 2 diabetes: the Collaborative Atorvastatin Diabetes Study (CARDS)

Article

The risk allele load accelerates the age-dependent decline in beta cell function
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits