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NIH Research Festival

September 14 – 16, 2016

Regulation of pancreatic islet β-cell proliferation

Wednesday, September 14, 2016 – Poster Session I
3:00 – 4:30 p.m.

FAES Terrace

NIDDK

CANCER-24

Authors

  • SS Kharade
  • SK Agarwal

Abstract

Studying the molecular basis underlying pancreatic islet β-cell proliferation can advance our knowledge of diseases associated with β-cell gain (as in the case of pancreatic neuroendocrine tumors, PNETs) or with β-cell loss (as in the case of diabetes). In contrast to non-functioning PNETs, the functioning PNETs (insulin secreting β-cell tumors, insulinomas) are rarely caused from loss of the MEN1 gene encoded tumor suppressor protein menin. However, insulinomas are frequently observed in mouse models of Men1 gene loss. Therefore, in order to identify the underlying cause of insulinomas in humans, we studied the targets and pathways downstream of menin as possible candidates for insulinoma development. One such target of menin that we have identified is the β-cell-specific transcription factor HB9 (also known as HLXB9 or MNX1). The phosphorylated form of HB9 in insulinoma cells interacted with a survival factor, p54nrb/Nono through the 160-240 amino acid region of HB9. This region could be used to design a synthetic peptide to disrupt the endogeneous HB9/Nono interaction and to study the impact on β-cell proliferation. The importance of phospho-HB9 is also reflected in one of two clinical mutations of HB9 in patients with juvenile diabetes, p.F248L and p.F272L. We found that HB9 p.F248L mutant localizes to the nucleus but lacks phosphorylation. Our studies implicate therapeutic strategies for either reducing β-cell proliferation in insulinomas or alleviating β-cell loss in diabetes through the modulation of HB9 phosphorylation and its interaction with Nono.

Scientific Focus Area: Cancer Biology

This page was last updated on Friday, March 26, 2021

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2016 program

Download the 2016 Research Festival Schedule Overview (6 pages)

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Current Research Festival

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  • 2024
    • General Schedule of Events
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    • Special Wednesday Events
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  • 2023
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