4.7 Article

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

Journal

DIABETES
Volume 62, Issue 10, Pages 3459-3468

Publisher

AMER DIABETES ASSOC
DOI: 10.2337/db12-1833

Keywords

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Funding

  1. National Institutes of Health [R01-DK-44523, P30-DK-36836]
  2. Joslin Diabetes and Endocrinology Research Center (DERC) Advanced Microscopy Core
  3. JDRF [1-2008-45]
  4. Diabetes Research and Wellness Foundation
  5. Daiichi Sankyo Foundation
  6. Ministry of Health, Labor and Welfare of Japan [11103401]

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Pancreatic duodenal homeobox-1 (Pdx1), a transcription factor required for pancreatic development and maintenance of -cell function, was assessed for a possible role in postnatal -cell formation from progenitors in the pancreatic ducts by selectively deleting Pdx1 from the ducts. Carbonic anhydrase II (CAII)(Cre);Pdx1(Fl) 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 -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 -cells but is essential for their full maturation to glucose-responsive -cells.

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