PDX1 in Ducts Is Not Required for Postnatal Formation of β-Cells but Is Necessary for Their Subsequent Maturation

  1. Susan Bonner-Weir1
  1. 1Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts
  2. 2Diabetes and Genes, Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  3. 3Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee.
  1. Corresponding author: Susan Bonner-Weir, susan.bonner-weir{at}joslin.harvard.edu.
  1. L.G. and A.I. contributed equally to this work.

Abstract

Pancreatic duodenal homeobox-1 (Pdx1), a transcription factor required for pancreatic development and maintenance of β-cell function, was assessed for a possible role in postnatal β-cell formation from progenitors in the pancreatic ducts by selectively deleting Pdx1 from the ducts. Carbonic anhydrase II (CAII)Cre;Pdx1Fl mice were euglycemic for the first 2 postnatal weeks but showed moderate hyperglycemia from 3 to 7 weeks of age. By 10 weeks, they had near-normal morning fed glucose levels but showed severely impaired glucose tolerance and insulin secretion. Yet the loss of Pdx1 did not result in decreased islet and β-cell mass at 4 and 10 weeks of age. Within the same pancreas, there was a mixed population of islets, with PDX1 and MAFA protein expression normal in some cells and severely diminished in others. Even at 10 weeks, islets expressed immaturity markers. Thus, we conclude that Pdx1 is not necessary for the postnatal formation of β-cells but is essential for their full maturation to glucose-responsive β-cells.

Footnotes

  • Received December 28, 2012.
  • Accepted June 12, 2013.

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  1. Diabetes vol. 62 no. 10 3459-3468
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