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A Pdx-1-Regulated Soluble Factor Activates Rat and Human Islet Cell Proliferation.

Publication ,  Journal Article
Hayes, HL; Zhang, L; Becker, TC; Haldeman, JM; Stephens, SB; Arlotto, M; Moss, LG; Newgard, CB; Hohmeier, HE
Published in: Mol Cell Biol
December 1, 2016

The homeodomain transcription factor Pdx-1 has important roles in pancreas and islet development as well as in β-cell function and survival. We previously reported that Pdx-1 overexpression stimulates islet cell proliferation, but the mechanism remains unclear. Here, we demonstrate that overexpression of Pdx-1 triggers proliferation largely by a non-cell-autonomous mechanism mediated by soluble factors. Consistent with this idea, overexpression of Pdx-1 under the control of a β-cell-specific promoter (rat insulin promoter [RIP]) stimulates proliferation of both α and β cells, and overexpression of Pdx-1 in islets separated by a Transwell membrane from islets lacking Pdx-1 overexpression activates proliferation in the untreated islets. Microarray and gene ontology (GO) analysis identified inhibin beta-B (Inhbb), an activin subunit and member of the transforming growth factor β (TGF-β) superfamily, as a Pdx-1-responsive gene. Overexpression of Inhbb or addition of activin B stimulates rat islet cell and β-cell proliferation, and the activin receptors RIIA and RIIB are required for the full proliferative effects of Pdx-1 in rat islets. In human islets, Inhbb overexpression stimulates total islet cell proliferation and potentiates Pdx-1-stimulated proliferation of total islet cells and β cells. In sum, this study identifies a mechanism by which Pdx-1 induces a soluble factor that is sufficient to stimulate both rat and human islet cell proliferation.

Duke Scholars

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

December 1, 2016

Volume

36

Issue

23

Start / End Page

2918 / 2930

Location

United States

Related Subject Headings

  • Trans-Activators
  • Rats
  • Promoter Regions, Genetic
  • Oligonucleotide Array Sequence Analysis
  • Islets of Langerhans
  • Insulin-Secreting Cells
  • Insulin
  • Inhibin-beta Subunits
  • Humans
  • Homeodomain Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Hayes, H. L., Zhang, L., Becker, T. C., Haldeman, J. M., Stephens, S. B., Arlotto, M., … Hohmeier, H. E. (2016). A Pdx-1-Regulated Soluble Factor Activates Rat and Human Islet Cell Proliferation. Mol Cell Biol, 36(23), 2918–2930. https://doi.org/10.1128/MCB.00103-16
Hayes, Heather L., Lu Zhang, Thomas C. Becker, Jonathan M. Haldeman, Samuel B. Stephens, Michelle Arlotto, Larry G. Moss, Christopher B. Newgard, and Hans E. Hohmeier. “A Pdx-1-Regulated Soluble Factor Activates Rat and Human Islet Cell Proliferation.Mol Cell Biol 36, no. 23 (December 1, 2016): 2918–30. https://doi.org/10.1128/MCB.00103-16.
Hayes HL, Zhang L, Becker TC, Haldeman JM, Stephens SB, Arlotto M, et al. A Pdx-1-Regulated Soluble Factor Activates Rat and Human Islet Cell Proliferation. Mol Cell Biol. 2016 Dec 1;36(23):2918–30.
Hayes, Heather L., et al. “A Pdx-1-Regulated Soluble Factor Activates Rat and Human Islet Cell Proliferation.Mol Cell Biol, vol. 36, no. 23, Dec. 2016, pp. 2918–30. Pubmed, doi:10.1128/MCB.00103-16.
Hayes HL, Zhang L, Becker TC, Haldeman JM, Stephens SB, Arlotto M, Moss LG, Newgard CB, Hohmeier HE. A Pdx-1-Regulated Soluble Factor Activates Rat and Human Islet Cell Proliferation. Mol Cell Biol. 2016 Dec 1;36(23):2918–2930.

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

December 1, 2016

Volume

36

Issue

23

Start / End Page

2918 / 2930

Location

United States

Related Subject Headings

  • Trans-Activators
  • Rats
  • Promoter Regions, Genetic
  • Oligonucleotide Array Sequence Analysis
  • Islets of Langerhans
  • Insulin-Secreting Cells
  • Insulin
  • Inhibin-beta Subunits
  • Humans
  • Homeodomain Proteins