Endocrine pancreatic tissue plasticity in obese humans is associated with cytoplasmic expression of PBX-1 in pancreatic ductal cells

Biochem Biophys Res Commun. 2005 Aug 12;333(4):1153-9. doi: 10.1016/j.bbrc.2005.05.199.

Abstract

In vivo lineage tracing experiments in mice have recently cast doubt on the potential islet neogenesis from ductal precursors in adult mammals. We examined, in human obesity, a model for pancreatic endocrine tissue plasticity, the gene and protein expression of PBX-1-a transcription factor expressed in regenerating rat ductules and potentially implicated in the pancreatic development, alone or in association with PDX-1. When comparing gene expression, by quantitative real-time RT-PCR, in pancreatic exocrine tissue from obese non-diabetic subjects with increased islet mass, we found that Pbx-1 and Pdx-1 were up-regulated (5.9+/-1.2 and 2.4+/-0.6 versus non-obese). Immunohistochemistry confirmed PBX-1 over-expression and its cytoplasmic sequestration in ductal cells of obese subjects, associated with pronounced islet neogenesis (cytokeratin 19/chromogranin A double labeling). cDNA microarray analysis also showed up-regulation of other genes implicated in islet regeneration, including betacellulin, laminin, TGFa, NeuroD1, Pax6, substantiating the role of the islet neogenesis pathway in human obesity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Cadaver
  • Cells, Cultured
  • Cytoplasm / metabolism
  • Cytoplasm / pathology
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Homeodomain Proteins / metabolism*
  • Humans
  • In Vitro Techniques
  • Obesity / metabolism*
  • Obesity / pathology*
  • Pancreatic Ducts / metabolism*
  • Pancreatic Ducts / pathology*
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Proto-Oncogene Proteins / metabolism*
  • Regeneration*
  • Tissue Distribution
  • Trans-Activators / metabolism*

Substances

  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Proto-Oncogene Proteins
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • pbx1 protein, human