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Nuclear orphan receptor TLX affects gene expression, proliferation and cell apoptosis in beta cells

Xiaoli Shi1, Xiaokan Xiong1, Zhe Dai1

  • 1Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, PR China.

Biochemical and Biophysical Research Communications
|October 17, 2015
PubMed

Insights

Nuclear orphan receptor TLX promotes beta cell proliferation and survival. Overexpression of TLX in MIN6 cells increased cell division and reduced apoptosis without affecting insulin secretion, suggesting therapeutic potential for diabetes.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Biology

Background:

  • Nuclear orphan receptor TLX (ten-eleven translocation 2) is crucial for neural stem cell development.
  • The role of TLX in pancreatic islet beta cells remains largely uncharacterized.

Purpose of the Study:

  • To investigate the function of TLX in pancreatic beta cell proliferation, apoptosis, and insulin secretion.
  • To explore the potential of TLX as a therapeutic target for diabetes.

Main Methods:

  • Gene expression profiling of MIN6 beta cells overexpressing TLX.
  • EdU incorporation assay to assess cell proliferation.
  • Cell cycle analysis and apoptosis assays (e.g., using palmitate-induced apoptosis).
  • Insulin secretion assays.

Main Results:

  • Overexpression of TLX modulated the expression of 176 suppressed and 49 upregulated genes in MIN6 cells, including cell cycle and apoptosis regulators.
  • TLX overexpression significantly increased MIN6 cell proliferation (EdU-positive cells).
  • TLX enhanced cell cycle progression from G1 to S-phase and reduced palmitate-induced apoptosis by 58.8%.
  • TLX overexpression did not impair insulin secretion from MIN6 cells.

Conclusions:

  • TLX plays a significant role in regulating pancreatic beta cell proliferation and survival.
  • TLX represents a potential therapeutic target for enhancing beta cell function and treating diabetes.
Keywords:
ApoptosisBeta cellCell proliferationDigital gene expression profileTLX

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