Pancreatic Duodenal Homeobox (PDX-1) in health and disease

Danielle Melloul*, Anat Tsur, David Zangen

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations


Insulin is expressed exclusively in the adult β-cells of the islets of Langerhans. Pancreatic Duodenum Homeobox-1 (PDX-1) is a major regulator of transcription in these cells. It transactivates the insulin gene by binding to a specific DNA motif in its promoter region. Glucose, the main physiological regulator of insulin secretion, also regulates insulin gene transcription through PDX-1. While acute exposure to high glucose concentrations causes an increase in PDX-1 binding, and consequently in insulin mRNA levels, chronic hyperglycemia (toxic to the β-cell) leads to a decrease in PDX-1 and insulin levels. PDX-1 is absolutely required for pancreas development. In view of the selective expression in adult β-cells, pancreatic agenesis in both the pdx-1 null mouse and a human carrying a homozygous mutation of PDX-1 was an unexpected and remarkable finding. The homozygous clinical phenotype was neonatal diabetes mellitus (DM) and exocrine insufficiency. Heterozygosity for PDX-1 mutations was found in some individuals with a newly characterized subtype of maturity-onset diabetes of the young (MODY4) and in others with type 2 DM. This review underlines the unique role of PDX-1 in maintaining adult β-cell-specific functions in normal and disease-related states.

Original languageAmerican English
Pages (from-to)1461-1472
Number of pages12
JournalJournal of Pediatric Endocrinology and Metabolism
Issue number9
StatePublished - 2002
Externally publishedYes

Bibliographical note

Funding Information:
We wish to express our gratitude to all members of the laboratory in the Department of Endocrinology, and principally to Sonya Marshak. Our sincere thanks to Dr. Leora Havin for valuable suggestions and for critically reading the manuscript. We would like to apologize to all the researchers whose work could not be cited. D.M. is supported by the Juvenile Research Foundation International (1-2001-325).


  • Gene regulation
  • Gene transcription
  • Insulin
  • MODY4
  • PDX-1
  • Pancreas development
  • Type 2 diabetes mellitus


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