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Glucagon contributes to liver zonation.

Xiping Cheng1, Sun Y Kim1, Haruka Okamoto1

  • 1Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.

Proceedings of the National Academy of Sciences of the United States of America
|March 21, 2018
PubMed
Summary
This summary is machine-generated.

Glucagon opposes Wnt/β-catenin signaling to regulate liver zonation and gene expression. This counterplay is crucial for maintaining the liver's metabolic zonation pattern and optimal function.

Keywords:
Wntglucagonglucagon receptorliver zonation

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Area of Science:

  • Hepatology
  • Molecular Biology
  • Metabolic Regulation

Background:

  • Liver zonation, the spatial segregation of metabolic functions within hepatic lobules, is essential for optimal liver physiology.
  • Wnt/β-catenin signaling is a key regulator, driving gene expression in perivenous hepatocytes and suppressing it in periportal hepatocytes.

Purpose of the Study:

  • To investigate the role of glucagon in modulating liver zonation and gene expression.
  • To elucidate the interplay between glucagon and Wnt/β-catenin signaling in hepatic metabolic zonation.

Main Methods:

  • Analysis of gene expression patterns in response to glucagon and Wnt/β-catenin signaling.
  • Assessment of receptor distribution and signaling pathway regulation.

Main Results:

  • Glucagon antagonizes Wnt/β-catenin signaling, impacting gene expression and metabolic zonation.
  • Significant gene expression changes were observed, particularly in periportal hepatocytes, where 28% of genes were activated by glucagon and inhibited by Wnt/β-catenin.
  • Receptors and signaling pathways for both glucagon and Wnt/β-catenin are uniformly distributed and not regulated by the opposing signal.

Conclusions:

  • Glucagon plays a critical role in controlling liver gene expression and metabolic zonation.
  • A counterplay between glucagon and Wnt/β-catenin signaling pathways dictates hepatic metabolic zonation patterns.