Insulin stimulates expression of the pyruvate kinase M gene in 3T3-L1 adipocytes

Yuuki Asai1, Kazuya Yamada, Toyoaki Watanabe

  • 1Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Chikusa.ku, Nagoya 464-8601, Japan.

Insights

Insulin boosts M2-type pyruvate kinase (M2-PK) mRNA in adipocytes via PI3K and MAPK signaling. This regulation occurs at both transcriptional and post-transcriptional levels, impacting M2-PK mRNA production.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Metabolism

Background:

  • M2-type pyruvate kinase (M2-PK) mRNA is generated through alternative splicing of the PKM gene in adipocytes.
  • Understanding the regulation of M2-PK mRNA is crucial for comprehending adipocyte function and metabolism.

Purpose of the Study:

  • To investigate the effect of insulin on M2-PK mRNA levels in adipocytes.
  • To elucidate the signaling pathways involved in insulin-mediated M2-PK mRNA regulation.

Main Methods:

  • Utilized 3T3-L1 adipocytes for experiments.
  • Administered insulin and measured M2-PK mRNA levels.
  • Employed pharmacological inhibitors (wortmannin, PD98059) of PI3K and MAPK pathways.
  • Conducted a stable reporter expression assay to assess PKM gene promoter activity.

Main Results:

  • Insulin significantly increased M2-PK mRNA levels in adipocytes in a time- and dose-dependent manner.
  • The insulin-induced increase in M2-PK mRNA was independent of glucose or glucosamine.
  • Inhibition of PI3K (wortmannin) and MAPK kinase (PD98059) blocked the insulin effect.
  • Insulin stimulated PKM gene promoter activity, but to a lesser extent than mRNA stimulation.

Conclusions:

  • Insulin elevates M2-PK mRNA levels in adipocytes through both transcriptional and post-transcriptional mechanisms.
  • The PI3K and MAPK kinase signaling pathways are essential for insulin's regulation of M2-PK mRNA.
  • These findings highlight a novel role for insulin in modulating M2-PK expression in adipocytes.

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