Downregulation of GLP-1 and GIP Receptor Expression by Hyperglycemia: Possible Contribution to Impaired Incretin Effects in Diabetes

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.

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

10.2337/figshare.14748642.v1 ◽

2021 ◽

Author(s):

Mette Q. Ludwig ◽

Petar V. Todorov ◽

Kristoffer L. Egerod ◽

David P. Olson ◽

Tune H. Pers

Keyword(s):

Single Cell ◽

Area Postrema ◽

Critical Role ◽

Receptor Expression ◽

Motor Nucleus ◽

Dorsal Vagal Complex ◽

Dorsal Motor Nucleus ◽

Glucagon Like Peptide 1 ◽

Mapping Techniques ◽

Gip Receptor

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.

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Plasticity of glucose‐dependent insulinotropic polypeptide (GIP) receptor expression in the vasculature

The FASEB Journal ◽

10.1096/fasebj.25.1_supplement.1070.3 ◽

2011 ◽

Vol 25 (S1) ◽

Author(s):

Lisa M Berglund ◽

Olga Kotova ◽

Isabel Goncalves ◽

Timothy J Kieffer ◽

Valeriya Lyssenko ◽

...

Keyword(s):

Receptor Expression ◽

Gip Receptor

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

10.2337/figshare.14748642.v2 ◽

2021 ◽

Author(s):

Mette Q. Ludwig ◽

Petar V. Todorov ◽

Kristoffer L. Egerod ◽

David P. Olson ◽

Tune H. Pers

Keyword(s):

Single Cell ◽

Area Postrema ◽

Critical Role ◽

Receptor Expression ◽

Motor Nucleus ◽

Dorsal Vagal Complex ◽

Dorsal Motor Nucleus ◽

Glucagon Like Peptide 1 ◽

Mapping Techniques ◽

Gip Receptor

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.

Download Full-text