A feat of metabolic proportions: Pdx1 orchestrates islet development and function in the maintenance of glucose homeostasis

Daniella A. Babu, Tye G. Deering, Raghavendra G. Mirmira

Research output: Contribution to journalReview article

60 Scopus citations

Abstract

Emerging evidence over the past decade indicates a central role for transcription factors in the embryonic development of pancreatic islets and the consequent maintenance of normal glucose homeostasis. Pancreatic and duodenal homeobox 1 (Pdx1) is the best studied and perhaps most important of these factors. Whereas deletion or inactivating mutations of the Pdx1 gene causes whole pancreas agenesis in both mice and humans, even haploinsufficiency of the gene or alterations in its expression in mature islet cells causes substantial impairments in glucose tolerance and the development of a late-onset form of diabetes known as maturity onset diabetes of the young. The study of Pdx1 has revealed crucial phenotypic interrelationships of the varied cell types within the pancreas, particularly as these impinge upon cellular differentiation in the embryo and neogenesis and regeneration in the adult. In this review, we describe the actions of Pdx1 in the developing and mature pancreas and attempt to unify these actions with its known roles in modulating transcriptional complex formation and chromatin structure at the molecular genetic level.

Original languageEnglish (US)
Pages (from-to)43-55
Number of pages13
JournalMolecular Genetics and Metabolism
Volume92
Issue number1-2
DOIs
StatePublished - Sep 1 2007

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Keywords

  • Cellular differentiation
  • Development
  • Diabetes
  • Glucose intolerance
  • Insulin
  • Islet
  • Neogenesis
  • Pancreas
  • Regeneration
  • Transcription
  • Transcription factor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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