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The effects of glipizide on DNA damage and nuclear transport in differentiated 3T3-L1 adipocytes

Mehtap Cevik1, Selen Caker1, Gokce Deliorman2

  • 1Division of Biology, Department of Molecular Biology, Faculty of Arts and Sciences, Marmara University, Istanbul, Turkey.

Molecular Biology Reports
|January 11, 2022
PubMed
Abstract

Insights

Glipizide, used for type II diabetes, causes DNA damage in mature and senescent adipocytes. Ran gene expression is altered by glipizide, with damage increasing with senescence.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Glipizide is a common type II diabetes medication.
  • Its effects on nuclear transport and DNA damage are not well understood.
  • Aging may alter glipizide's clinical response.

Purpose of the Study:

  • To investigate glipizide's effects on mature and senescent adipocytes.
  • To compare glipizide's impact on DNA damage and gene expression in different aged cells.

Main Methods:

  • 3T3-L1 adipocytes were used.
  • Real-time monitoring (iCELLigence) determined effective and lethal doses.
  • Comet assay assessed DNA damage.
  • Quantitative PCR measured gene expression (RAN).

Main Results:

  • Glipizide (180 µM) upregulated RAN expression in mature adipocytes but downregulated it in senescent adipocytes.
  • Significant DNA damage (Olive Tail Moment) was observed in both mature and senescent adipocytes treated with glipizide.
  • Higher levels of severe DNA damage (class 5 comets) were found in treated cells, with greater damage in senescent cells.

Conclusions:

  • This study is the first to report glipizide-induced DNA damage that increases with adipocyte senescence.
  • Glipizide alters RAN gene expression differently in mature versus senescent adipocytes.
  • Further research is necessary to elucidate glipizide's molecular interactions with DNA and nuclear transport.
Keywords:
3T3-L1 adipocytesDNA damageGlipizideNuclear transportRAN gene

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