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Updated: Feb 19, 2026

Utilizing a Comprehensive Immunoprecipitation Enrichment System to Identify an Endogenous Post-translational Modification Profile for Target Proteins
08:12

Utilizing a Comprehensive Immunoprecipitation Enrichment System to Identify an Endogenous Post-translational Modification Profile for Target Proteins

Published on: January 8, 2018

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IRS posttranslational modifications in regulating insulin signaling

Jinghua Peng1,2, Ling He3

  • 1Division of Metabolism and EndocrinologyDepartments of Pediatrics and Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Journal of Molecular Endocrinology
|November 3, 2017
PubMed

Insights

Elevated endotoxin in obese mice induces P300 acetyltransferase, impairing insulin signaling by modifying IRS1/2. Targeting P300 may treat type 2 diabetes.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • Insulin resistance is central to type 2 diabetes, but its mechanisms are unclear.
  • Posttranslational modifications of insulin receptor substrate (IRS) are crucial for insulin signaling.
  • Sirtuin 1 enhances insulin sensitivity, but its opposing acetyltransferase remains unidentified.

Purpose of the Study:

  • To identify the acetyltransferase involved in insulin resistance.
  • To investigate the role of endotoxin (LPS) and the IRE1-XBP1s pathway in this process.
  • To explore P300 as a potential therapeutic target for diabetes.

Main Methods:

  • Utilized obese mouse models with elevated liver endotoxin (LPS) levels.
  • Investigated the IRE1-XBP1s pathway activation.
  • Assessed the acetylation of IRS1 and IRS2 by P300.
  • Analyzed insulin signaling pathway function.

Main Results:

  • Elevated LPS levels in obese mice induced P300 expression via the IRE1-XBP1s pathway.
  • Induced P300 acetylated IRS1 and IRS2, impairing insulin signaling.
  • P300 activity was directly linked to insulin resistance in this model.

Conclusions:

  • The P300 acetyltransferase, induced by LPS through IRE1-XBP1s, contributes to insulin resistance.
  • P300-mediated acetylation of IRS proteins is a key mechanism in diabetes development.
  • Inhibiting P300 activity presents a potential therapeutic strategy for type 2 diabetes.
Keywords:
diabetes IIinsulin actioninsulin receptorinsulin signalingliver

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