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Adrenergic Agonists: Therapeutic Uses01:30

Adrenergic Agonists: Therapeutic Uses

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Adrenergic agonists have diverse therapeutic uses across various medical conditions and emergencies.
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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
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Adrenergic Agonists: Therapeutic Classification01:18

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Tomography refers to imaging by sections. Computed tomography (CT) is a non-invasive imaging technique that uses computers to analyze several cross-sectional X-rays to reveal minute details about structures in the body.
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Direct-acting cholinergic agonists, such as synthetic choline esters and naturally occurring alkaloids, exert their effects by enhancing the actions of acetylcholine and stimulating the parasympathetic nervous system. Synthetic choline esters share structural similarities with acetylcholine. For example, they have a positively charged quaternary ammonium or onium group, contributing to their hydrophilic characteristics. As a result, they are poorly absorbed in the body through oral...
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Computationally identified novel agonists for GPRC6A.

Min Pi1, Karan Kapoor2, Ruisong Ye1

  • 1Department of Medicine, University of Tennessee Health Science Center, Tennessee, United States of America.

Plos One
|April 24, 2018
PubMed
Summary
This summary is machine-generated.

Researchers identified G protein-coupled receptor class C group 6 member A (GPRC6A) as a promising target for type 2 diabetes mellitus (T2D). Activating GPRC6A with novel compounds may improve glucose control and insulin function.

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Quantifying Agonist Activity at G Protein-coupled Receptors
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Area of Science:

  • Endocrinology
  • Pharmacology
  • Metabolic Diseases

Background:

  • G protein-coupled receptors (GPCRs) play crucial roles in regulating glucose metabolism.
  • Type 2 diabetes mellitus (T2D) involves complex metabolic dysregulation, including impaired insulin secretion and peripheral insulin resistance.
  • Identifying novel therapeutic targets for T2D is a significant unmet medical need.

Purpose of the Study:

  • To identify and validate G protein-coupled receptor class C group 6 member A (GPRC6A) as a therapeutic target for T2D.
  • To discover small molecule agonists for GPRC6A.
  • To evaluate the efficacy of GPRC6A activation in preclinical models of T2D.

Main Methods:

  • Computational, structure-based high-throughput screening to identify GPRC6A ligands.
  • In vitro functional assays to assess GPRC6A signaling and insulin secretion.
  • In vivo studies in wild-type mice to evaluate glucose-lowering effects.

Main Results:

  • Novel tri-phenyl compounds were identified that bind to GPRC6A.
  • These compounds dose-dependently stimulated GPRC6A signaling in a heterologous system.
  • Lead compound DJ-V-159 enhanced insulin secretion and lowered serum glucose in vivo.

Conclusions:

  • GPRC6A is a druggable target for T2D.
  • Activation of GPRC6A holds potential for a new therapeutic strategy for T2D.
  • DJ-V-159 represents a promising chemical probe for further T2D drug development.