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

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posted on 25.06.2021, 00:33 by Mette Q. Ludwig, Petar V. Todorov, Kristoffer L. Egerod, David P. Olson, Tune H. Pers
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 are 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 circuits in the hindbrain.

Funding

Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research centre, based at the University of Copenhagen, and partially funded by an unconditional donation from the Novo Nordisk Foundation (https://www.cbmr.ku.dk/; grant no. NNF18CC0034900). We acknowledge the Novo Nordisk Foundation (grant no. NNF16OC0021496 to T.H.P.) and the Lundbeck Foundation (grant no. R190-2014-3904 to T.H.P.). We also acknowledge The Single-Cell Omics Platform at the Novo Nordisk Foundation Center for Basic Metabolic Research for technical expertise and support. Furthermore, this work was supported by a research grant from the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation (grant no. NNF17SA0031406). Finally, this work has been supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grant no. R01 DK104999 and P01 DK117821).

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