Glucagon-like peptide-1 receptor: mechanisms and advances in therapy

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Сен. 18, 2024

The glucagon-like peptide-1 (GLP-1) receptor, known as GLP-1R, is a vital component of the G protein-coupled receptor (GPCR) family and found primarily on surfaces various cell types within human body. This specifically interacts with GLP-1, key hormone that plays an integral role in regulating blood glucose levels, lipid metabolism, several other crucial biological functions. In recent years, GLP-1 medications have become focal point medical community due to their innovative treatment mechanisms, significant therapeutic efficacy, broad development prospects. article thoroughly traces developmental milestones drugs, from initial discovery clinical application, detailing evolution diverse along distinct pharmacological properties. Additionally, this paper explores potential applications agonists (GLP-1RAs) fields such neuroprotection, anti-infection measures, reduction inflammation, enhancement cardiovascular function. It provides in-depth assessment effectiveness GLP-1RAs across multiple body systems-including nervous, cardiovascular, musculoskeletal, digestive systems. includes integrating latest trial data delving into signaling pathways mechanisms. primary goal emphasize extensive benefits using treating spectrum diseases, obesity, non-alcoholic fatty liver disease (NAFLD), neurodegenerative musculoskeletal forms cancer. ongoing new indications for drugs offers promising prospects further expanding interventions, showcasing field.

Язык: Английский

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Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Март 5, 2025

The successful approval of peptide-based drugs can be attributed to a collaborative effort across multiple disciplines. integration novel drug design and synthesis techniques, display library technology, delivery systems, bioengineering advancements, artificial intelligence have significantly expedited the development groundbreaking drugs, effectively addressing obstacles associated with their character, such as rapid clearance degradation, necessitating subcutaneous injection leading increasing patient discomfort, ultimately advancing translational research efforts. Peptides are presently employed in management diagnosis diverse array medical conditions, diabetes mellitus, weight loss, oncology, rare diseases, additionally garnering interest facilitating targeted platforms advancement vaccines. This paper provides an overview present market clinical trial progress therapeutics, platforms, It examines key areas through literature analysis emphasizes structural modification principles well recent advancements screening, design, technologies. accelerated including peptide-drug complexes, new vaccines, innovative diagnostic reagents, has potential promote era precise customization disease therapeutic schedule.

Язык: Английский

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Recent advances, strategies, and future perspectives of peptide-based drugs in clinical applications

Chinese Journal of Natural Medicines, Год журнала: 2025, Номер 23(1), С. 31 - 42

Опубликована: Янв. 1, 2025

Язык: Английский

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New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(8), С. 4407 - 4407

Опубликована: Апрель 17, 2024

This review examines the impact of obesity on pathophysiology heart failure with preserved ejection fraction (HFpEF) and focuses novel mechanisms for HFpEF prevention using a glucagon-like peptide-1 receptor agonism (GLP-1 RA). Obesity can lead to through various mechanisms, including low-grade systemic inflammation, adipocyte dysfunction, accumulation visceral adipose tissue, increased pericardial/epicardial tissue (contributing an increase in myocardial fat content interstitial fibrosis). Glucagon-like peptide 1 (GLP-1) is incretin hormone that released from enteroendocrine L-cells gut. GLP-1 reduces blood glucose levels by stimulating insulin synthesis, suppressing islet α-cell function, promoting proliferation differentiation β-cells. regulates gastric emptying appetite, RA currently indicated treating type 2 diabetes (T2D), obesity, metabolic syndrome (MS). Recent evidence indicates may play significant role preventing patients MS, or obese T2D. effect be due activating cardioprotective (the endogenous counter-regulatory renin angiotensin system AMPK/mTOR pathway) inhibiting deleterious remodeling PKA/RhoA/ROCK pathway, aldosterone levels, microinflammation). However, there still need further research validate these humans.

Язык: Английский

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Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide

Cell Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Июль 17, 2024

Язык: Английский

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The Power of Three: Retatrutide’s Role in Modern Obesity and Diabetes Therapy

European Journal of Pharmacology, Год журнала: 2024, Номер 985, С. 177095 - 177095

Опубликована: Ноя. 6, 2024

Язык: Английский

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GLP-1 receptor agonists in patients with chronic kidney disease and either overweight or obesity

Clinical Kidney Journal, Год журнала: 2024, Номер 17(Supplement_2), С. 19 - 35

Опубликована: Ноя. 22, 2024

ABSTRACT Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as game-changers across the cardiovascular–kidney–metabolic (CKM) spectrum: overweight/obesity, type 2 diabetes mellitus (T2DM) and associated chronic kidney disease (CKD) cardiovascular (CVD). Liraglutide, semaglutide tirzepatide are European Medicines Agency approved to improve metabolic control in T2DM decrease weight persons with obesity [body mass index (BMI) ≥30 kg/m2] or overweight (BMI ≥27 kg/m2) weight-related comorbidities such hypertension, dyslipidaemia, CVD others. Additionally, liraglutide reduce risk patients T2DM. Semaglutide is also either phase 3 clinical trials showed protection albuminuric CKD (FLOW trial) well without that had overweight/obesity (SELECT trial). Thus, nephrologists should consider prescribing GLP-1 RAs control, outcomes three scenarios: a related comorbid condition dyslipidaemia CVD, This review addresses promising landscape of treat obesity, T2DM, within context CKD, assessing their safety impact on weight, blood pressure outcomes, part holistic patient-centred approach preserve CKM health.

Язык: Английский

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Innovative Drugs First Implemented in Type 2 Diabetes Mellitus and Obesity and Their Effects on Metabolic Dysfunction-Associated Steatohepatitis (MASH)-Related Fibrosis and Cirrhosis

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(4), С. 1042 - 1042

Опубликована: Фев. 7, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD), a progressive frequently associated with metabolic disorders such as type 2 diabetes mellitus (T2DM) and obesity, has the potential to progress symptomatically cirrhosis and, in some cases, hepatocellular carcinoma. Hence, an urgent need arises identify approve new therapeutic options improve patient outcomes. Research efforts have focused on either developing dedicated molecules or repurposing drugs already approved for other conditions, diseases. Among latter, antidiabetic anti-obesity agents received most extensive attention, pivotal trial results anticipated shortly. However, primary focus underlying successful regulatory approvals is demonstrating substantial efficacy improving fibrosis preventing ameliorating cirrhosis, key advanced outcomes within MASLD progression. Besides steatosis, ideal candidate should reduce inflammation effectively. Although shown promise lowering MASLD-related parameters, evidence of their impact remains limited. This review aims evaluate whether can be safely effectively used patients T2DM. Our paper discusses closest approval expectation that they address unmet needs this increasingly prevalent disease.

Язык: Английский

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

Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 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.

Язык: Английский

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Glucose-dependent insulinotropic peptide and beyond: co-agonist innovations in the treatment of metabolic diseases

European Journal of Pharmacology, Год журнала: 2025, Номер 999, С. 177681 - 177681

Опубликована: Апрель 28, 2025

Язык: Английский

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