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Improved glucose tolerance and acinar dysmorphogenesis by targeted expression of transcription factor PDX-1 to the

R S Heller1, D A Stoffers, T Bock

  • 1Department of Developmental Biology, Hagedorn Research Institute, DK 2820, Gentofte, Denmark. shll@hagedorn.dk

Diabetes
|June 26, 2001
PubMed

Insights

Overexpressing the pancreas duodenum homeobox 1 (PDX-1) protein in exocrine pancreas cells disrupts pancreas development. This leads to improved glucose tolerance but does not increase beta-cell mass.

Area of Science:

  • Developmental biology
  • Endocrinology
  • Genetics

Background:

  • The homeodomain protein PDX-1 is crucial for pancreas development and insulin gene regulation.
  • PDX-1 deficiency causes pancreatic agenesis and diabetes.
  • PDX-1 expression changes during pancreas development, decreasing in exocrine cells by embryonic day 15.

Purpose of the Study:

  • To investigate if overexpressing PDX-1 in the exocrine pancreas at embryonic day 15 can respecify exocrine cells.
  • To understand the role of PDX-1 downregulation in maintaining exocrine cell identity.

Main Methods:

  • Generation of transgenic (TG) mice with PDX-1 overexpression in the exocrine pancreas using the elastase-1 promoter.
  • Analysis of pancreatic morphology, cell replication, apoptosis, and glucose tolerance in TG mice.

Main Results:

  • TG mice showed significant exocrine pancreas dysmorphogenesis, including increased acinar cell replication and apoptosis.
  • Progressive fatty infiltration of the exocrine pancreas was observed with age in TG mice.
  • TG mice exhibited improved glucose tolerance, but beta-cell mass remained unchanged.

Conclusions:

  • Downregulation of PDX-1 is essential for maintaining the exocrine pancreas cell phenotype.
  • Upregulation of PDX-1 in acinar cells impacts beta-cell function.
  • The precise mechanisms require further investigation.

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