Endocrine pancreatic tissue plasticity in obese humans is associated with cytoplasmic expression of PBX-1 in pancreatic ductal cells.
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.
Cell Therapy of Diabetes, INSERM ERIT-M 0106, Faculty of Medicine, 1 Place de Verdun 59045 Lille, France.
Ghaffar
G
Muharram
Anthony
A
Beucher
Ericka
E
Moerman
Sandrine
S
Belaïch
Valéry
V
Gmyr
Brigitte
B
Vandewalle
Francois
F
Pattou
Julie
J
Kerr-Conte
D000222:Adaptation, Physiological; D002102:Cadaver; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009765:Obesity / Q000378:metabolism* / Q000473:pathology*; D010183:Pancreatic Ducts / Q000378:metabolism* / Q000473:pathology*; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012038:Regeneration; D014018:Tissue Distribution; D015534:Trans-Activators / Q000378:metabolism*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; C083400:PBX1 protein, human