Hormonal
Hypothalamic Glp1r-expressing cells are predominantly neuronal and localized to arterial vascular beds, whereas Gipr-expressing cells are predominantly non-neuronal (oligodendrocytes and pericytes) and localized to venous vascular beds.
This research suggests that GLP-1 and GIP drugs work through different pathways in the brain. GLP-1 primarily targets neurons and arterial blood vessels, while GIP targets support cells (oligodendrocytes) and venous blood vessels. This distinct localization may explain why combining them (dual agonism) is more effective for weight loss than using GLP-1 alone.
The majority of GiprEYFP+ cells were non-neuronal, whereas the Glp1rEYFP+ population was evenly split between neuronal and non-neuronal cell types... While mural cells are represented in both Glp1rEYFP+ and GiprEYFP+ populations, Glp1rEYFP+ mural cells are largely smooth muscle cells, while the majority of GiprEYFP+ mural cells are pericytes.
Why this rating
High-quality single-cell RNA sequencing data from transgenic mouse models, though translational to humans requires validation.
Source
A comparative transcriptomic analysis of glucagon-like peptide-1 receptor- and glucose-dependent insulinotropic polypeptide receptor-expressing cells in the hypothalamus
Christopher A. Smith et al. · Appetite · 2022
DOI 10.1016/j.appet.2022.106022
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