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Updated: Nov 18, 2025

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
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The Increased Expression of Regulator of G-Protein Signaling 2 (RGS2) Inhibits Insulin-Induced Akt Phosphorylation

J Gustavo Vazquez-Jimenez1,2, M Stephanie Corpus-Navarro2, J Miguel Rodriguez-Chavez2

  • 1Department of Biochemistry, Center for Research and Advanced Studies of the National Polytechnic Institute, CINVESTAV-IPN, Mexico City 07360, Mexico.

Metabolites
|February 10, 2021
PubMed

Insights

High regulator of G-protein signaling 2 (RGS2) protein levels are linked to insulin resistance in humans. Increased RGS2 expression impairs insulin signaling and is associated with type 2 diabetes mellitus.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Metabolic Diseases

Background:

  • High regulator of G-protein signaling 2 (RGS2) protein levels have been observed in mouse models preceding insulin resistance.
  • Saturated fatty acid-rich diets increase RGS2 expression and decrease basal metabolism in mice, but human data are lacking.

Purpose of the Study:

  • To investigate the association between RGS2 expression and insulin resistance in humans.
  • To explore the role of RGS2 in insulin signaling pathways.

Main Methods:

  • Incubation of human umbilical vein endothelial cells (HUVEC-CS) with palmitic acid (PA) to assess RGS2 expression and insulin signaling.
  • RGS2 overexpression experiments in HUVEC-CS cells.
  • Analysis of platelet RGS2 expression levels in type 2 diabetes mellitus (T2DM) patients and healthy donors.
  • Principal component analysis (PCA) to correlate RGS2 levels with clinical parameters (HbA1c, age, HDL).

Main Results:

  • Palmitic acid incubation increased RGS2 expression and inhibited insulin-mediated Akt Ser473 phosphorylation in HUVEC-CS cells.
  • RGS2 overexpression alone was sufficient to inhibit insulin-mediated Akt Ser473 phosphorylation.
  • Platelet RGS2 levels were significantly higher in T2DM patients compared to healthy individuals.
  • RGS2 expression positively correlated with HbA1c and negatively with age and HDL in T2DM patients.
  • PCA distinguished T2DM patients from healthy subjects based on lower HbA1c and RGS2 levels.

Conclusions:

  • RGS2 overexpression impairs insulin signaling in human endothelial cells.
  • Elevated RGS2 expression is associated with insulin resistance and poorly controlled type 2 diabetes mellitus in humans.
Keywords:
Akt proteinHbA1chuman endothelial cellsinsulin resistancepalmitic acidregulator of G-protein signaling 2type 2 diabetes mellitus

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