Regulation of GLP-1 and Glucagon Receptor Function by β-Arrestins in Metabolically Important Cell Types DOI
Liu Liu,

Muhammad Rashid,

Jürgen Wess

et al.

Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Glucagon-like peptide-1 (GLP-1) and glucagon (GCG) are polypeptides derived from a common precursor (preproglucagon) that modulates the activity of numerous cell types involved in regulating glucose energy homeostasis. GLP-1 GCG exert their biological functions via binding to specific G protein-coupled receptors (GLP-1Rs GCGRs). Ligand-activated GLP-1Rs GCGRs preferentially activate heterotrimeric protein Gs, resulting increased cytosolic cAMP levels. However, activation two also leads recruitment β-arrestin-1 -2 (βarr1 βarr2, respectively) intracellular surface receptor proteins. The β-arrestins activated contributes termination receptor-stimulated coupling. In addition, receptor-β-arrestin complexes can act as signaling nodes own right by modulating many pathways. this Review, we will discuss roles βarr1 βarr2 key metabolic mediated GCGRs. During past decade, GLP-1R agonists have emerged highly efficacious antidiabetic antiobesity drugs. Moreover, dual stimulate both predicted offer additional therapeutic benefits compared agonist monotherapy. We summarize try synthesize series studies suggesting development protein-biased and/or GCGR agonists, which do not lead β-arrestins, may even more agents.

Language: Английский

The Triad of Risk: Linking MASLD, Cardiovascular Disease and Type 2 Diabetes; From Pathophysiology to Treatment DOI Open Access
Eleni Michalopoulou, J Thymis, Stamatios Lampsas

et al.

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 428 - 428

Published: Jan. 10, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health concern, and it not only the keystone precursor of eventual liver-related morbidity, but also places patients at considerably higher cardiovascular risk, which still a leading cause death in these patients. The most important common underlying pathophysiological mechanisms diseases are primarily related to insulin resistance, chronic inflammation oxidative stress. presence MASLD with (CVD) type 2 diabetes mellitus (T2DM) elevates risk for poor outcomes, thus this review highlights method therapeutic approaches. Given intertwined nature MASLD, T2DM, CVD, there urgent need strategies that address all three conditions. Although lifestyle changes as treatment, medication plays crucial role managing hyperglycemia, enhancing function lowering risk. onset progression should be addressed through multifaceted approach, targeting inflammatory, immune, metabolic, stress, hormonal gutaxis pathways, alongside treatment T2DM. In review, we discuss effects antidiabetic drugs impact on both outcomes affected by T2DM CDV.

Language: Английский

Citations

1
Regulation of GLP-1 and Glucagon Receptor Function by β-Arrestins in Metabolically Important Cell Types DOI
Liu Liu,

Muhammad Rashid,

Jürgen Wess

et al.

Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Glucagon-like peptide-1 (GLP-1) and glucagon (GCG) are polypeptides derived from a common precursor (preproglucagon) that modulates the activity of numerous cell types involved in regulating glucose energy homeostasis. GLP-1 GCG exert their biological functions via binding to specific G protein-coupled receptors (GLP-1Rs GCGRs). Ligand-activated GLP-1Rs GCGRs preferentially activate heterotrimeric protein Gs, resulting increased cytosolic cAMP levels. However, activation two also leads recruitment β-arrestin-1 -2 (βarr1 βarr2, respectively) intracellular surface receptor proteins. The β-arrestins activated contributes termination receptor-stimulated coupling. In addition, receptor-β-arrestin complexes can act as signaling nodes own right by modulating many pathways. this Review, we will discuss roles βarr1 βarr2 key metabolic mediated GCGRs. During past decade, GLP-1R agonists have emerged highly efficacious antidiabetic antiobesity drugs. Moreover, dual stimulate both predicted offer additional therapeutic benefits compared agonist monotherapy. We summarize try synthesize series studies suggesting development protein-biased and/or GCGR agonists, which do not lead β-arrestins, may even more agents.

Language: Английский

Citations

0