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.
Muharram
Ghaffar
G
Cell Therapy of Diabetes, INSERM ERIT-M 0106, Faculty of Medicine, 1 Place de Verdun 59045 Lille, France.
Beucher
Anthony
A
Moerman
Ericka
E
Belaïch
Sandrine
S
Gmyr
Valéry
V
Vandewalle
Brigitte
B
Pattou
Francois
F
Kerr-Conte
Julie
J
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