4.7 Article

Single-Cell Mapping of GLP-1 and GIP Receptor Expression in the Dorsal Vagal Complex

Journal

DIABETES
Volume 70, Issue 9, Pages 1945-1955

Publisher

AMER DIABETES ASSOC
DOI: 10.2337/dbi21-0003

Keywords

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Funding

  1. Novo Nordisk Foundation [NNF18CC0034900, NNF16OC0021496]
  2. Lundbeck Foundation [R190-2014-3904]
  3. Danish Diabetes Academy - Novo Nordisk Foundation [NNF17SA0031406]
  4. National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK104999, P01 DK117821]

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The dorsal vagal complex (DVC) in the hindbrain plays a critical role in modulating satiety, with incretins like GLP-1 and GIP acting directly in the brain to regulate feeding through receptors expressed in the DVC. Single-cell approaches have been used to detect molecular signatures of incretin receptor-expressing cells in the DVC, and advancements in transcriptomics, epigenetics, spatial transcriptomics, and circuit mapping techniques hold potential for further characterizing incretin receptor circuits in the hindbrain.
The dorsal vagal complex (DVC) in the hindbrain, composed of the area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus, plays a critical role in modulating satiety. The incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) act directly in the brain to modulate feeding, and receptors for both are expressed in the DVC. Given the impressive clinical responses to pharmacologic manipulation of incretin signaling, understanding the central mechanisms by which incretins alter metabolism and energy balance is of critical importance. Here, we review recent single-cell approaches used to detect molecular signatures of GLP-1 and GIP receptor-expressing cells in the DVC. In addition, we discuss how current advancements in single-cell transcriptomics, epigenetics, spatial transcriptomics, and circuit mapping techniques have the potential to further characterize incretin receptor circuits in the hindbrain.

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