Differential effects of glucose‐dependent insulinotropic polypeptide receptor/glucagon‐like peptide‐1 receptor heteromerization on cell signaling when expressed in HEK‐293 cells

Sep 30, 2022Pharmacology research & perspectives

Different effects of combined glucose-dependent insulin and glucagon-like peptide receptors on cell signaling in lab-grown cells

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Abstract

GLP-1R and GIPR form heteromers that influence cell signaling in distinct ways.

  • Real-time fluorescence resonance energy transfer (FRET) and bioluminescence resonance energy transfer (BRET) experiments confirm the formation of GLP-1R and GIPR heteromers.
  • Stimulation with 1 μM GLP-1 increases both FRET and BRET ratios, indicating enhanced interaction.
  • Stimulation with 1 μM GIP decreases the BRET signal, suggesting a different interaction effect.
  • GIPR expression did not significantly affect the recruitment of certain signaling molecules to GLP-1R but inhibited GLP-1 stimulated recruitment.
  • The presence of GLP-1R enhanced GIP stimulated recruitment to GIPR, indicating a supportive role in signaling.

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Key numbers

1 μM GLP-1
Increase in BRET Ratio
Stimulation with GLP-1 resulted in a significant increase in BRET ratio.
1 μM GIP
Decrease in BRET Ratio
Stimulation with GIP resulted in a significant decrease in BRET ratio.

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