Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model

Area of Science:

• Metabolic research
• Endocrinology
• Neuroscience

Background:

• Glucagon-like peptide-1 (GLP-1) is an intestinal hormone impacting metabolism.
• GLP-1-based therapies are effective for type 2 diabetes by enhancing insulin secretion.
• GLP-1 may have diverse effects on multiple organs, necessitating identification of its receptor targets.

Purpose of the Study:

• To identify and characterize the tissue distribution of the GLP-1 receptor (GLP1R) in mice.
• To utilize a method independent of GLP1R antibodies for target identification.
• To inform the development of GLP-1-based therapeutic strategies.

Main Methods:

• Generation of novel glp1r-Cre mice.
• Crossing glp1r-Cre mice with fluorescent reporter strains.
• Analysis of GLP1R expression patterns across various tissues and neuronal populations.

Main Results:

• Major GLP1R expression sites identified in pancreatic β- and δ-cells, vascular smooth muscle, cardiac atrium, and gastric tissues.
• GLP1R was found in enteric neurons, vagal, and dorsal root ganglia.
• Abundant GLP1R expression in key central nervous system areas including the hypothalamus and area postrema.
• Enteric and vagal neurons expressing GLP1R were activated by GLP-1, suggesting roles in intestinal and central regulation.

Conclusions:

• GLP1R is expressed in a wider range of tissues than previously recognized, including key metabolic and neural circuits.
• The identified GLP1R distribution supports its role in regulating glucose homeostasis, appetite, and gastrointestinal function.
• Understanding GLP1R localization is critical for optimizing GLP-1-based therapies and exploring new therapeutic applications.