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Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
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The tyrosine phosphorylation of GRK2 is responsible for activated D2R-mediated insulin resistance

Zhenglin Gao1, Xiao Min2, Kyeong-Man Kim2

  • 1School of Pharmaceutical Sciences, Guizhou University, Guiyang, 550025, China.

Biochemical and Biophysical Research Communications
|September 5, 2022
PubMed

Insights

Dopamine D2 receptor (D2R) activation impairs glucose transport by inhibiting the PI3K/Akt pathway. This study reveals a novel mechanism linking D2R signaling to insulin resistance via GRK2 and Src.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Metabolic Research

Background:

  • Dopamine D2 receptor (D2R) influences glucose homeostasis and hormone secretion.
  • Insulin resistance (IR) is linked to PI3K/Akt pathway downregulation and metabolic disorders.

Purpose of the Study:

  • To investigate the role of D2-like receptors in regulating glucose transport.
  • To elucidate the molecular mechanisms by which D2R activation affects insulin signaling and contributes to insulin resistance.

Main Methods:

  • Investigated D2R, D3R, and D4R effects on insulin-induced 2-DOG uptake and Glut4 translocation.
  • Analyzed the impact of D2R activation on Akt phosphorylation (Thr308, Ser473).
  • Examined the interaction between GRK2, Src, Akt, and PDK1.

Main Results:

  • D2R activation, not D3R or D4R, suppressed insulin-induced 2-DOG uptake and Glut4 membrane translocation.
  • D2R activation inhibited insulin-induced Akt phosphorylation at Thr308 and Ser473.
  • D2R activation increased tyrosine phosphorylated GRK2 interaction with Akt, preventing Akt-PDK1 interaction.

Conclusions:

  • Dopamine D2 receptor activation contributes to insulin resistance.
  • Src-mediated GRK2 tyrosine phosphorylation is a key mechanism by which D2R activation inhibits insulin signaling and glucose transport.
Keywords:
Akt kinase activityDopamine D(2) receptorGRK2Insulin resistanceSrc

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