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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Anti-inflammatory role of glucagon-like peptide 1 receptor agonists and its clinical implications

Therapeutic Advances in Endocrinology and Metabolism, Год журнала: 2024, Номер 15

Опубликована: Янв. 1, 2024

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have emerged as promising therapeutic agents with potent anti-inflammatory properties and diverse clinical implications. This in-depth review article explores the mechanisms behind actions of GLP-1RAs assesses their prospective applicability in a wide range disease scenarios. The current establishes significance comprehending role identifies pertinent research gaps. A concise overview inflammation its consequences underscores critical need for effective interventions. Subsequently, elucidates intricate through which modulate immune cell signaling regulate nuclear factor-kappa B (NF-κB) pathway. Detailed discussions encompass impact on inflammatory responses, cytokine production, attenuation oxidative stress. exposition is substantiated by collection examples an extensive array references from both preclinical investigations. historical trajectory GLP-1RA drugs, including exenatide, lixisenatide, liraglutide, semaglutide, traced to delineate development agents. Moreover, emphasizes potential specific contexts like type 2 diabetes, neurodegenerative disorder, bowel (IBD), shedding light effects rigorous examination studies. also provides outlook future perspectives GLP-1RAs, encompassing domains diseases, IBD. In conclusion, exhibit substantial effects, rendering them broad They are very useful variety diseases because they immunological block NF-κB activation, decrease production pro-inflammatory cytokines. Ongoing endeavors aim optimize use, patient-specific treatment paradigms, explore novel applications. represent significant breakthrough therapy, offering options, improved patient outcomes.

Язык: Английский

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Association of GLP-1 Receptor Agonists and Hepatocellular Carcinoma Incidence and Hepatic Decompensation in Patients With Type 2 Diabetes

Gastroenterology, Год журнала: 2024, Номер 167(4), С. 689 - 703

Опубликована: Апрель 29, 2024

Hepatocellular carcinoma (HCC) is a leading cause of cancer death. HCC preventable with about 70% attributable to modifiable risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), Food and Drug Administration-approved medications for treating type 2 diabetes mellitus (T2DM), have pleiotropic effects on counteracting factors HCC. Here we evaluate the association GLP-1RAs incident in real-world population.

Язык: Английский

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Mechanisms of long COVID and the path toward therapeutics

Cell, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

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Glucagon-Like Peptide-1: New Regulator in Lipid Metabolism

Diabetes & Metabolism Journal, Год журнала: 2024, Номер 48(3), С. 354 - 372

Опубликована: Апрель 2, 2024

Glucagon-like peptide-1 (GLP-1) is a 30-amino acid peptide hormone that mainly expressed in the intestine and hypothalamus. In recent years, basic clinical studies have shown GLP-1 closely related to lipid metabolism, it can participate metabolism by inhibiting fat synthesis, promoting differentiation, enhancing cholesterol adipose browning. plays key role occurrence development of metabolic diseases such as obesity, nonalcoholic fatty liver disease, atherosclerosis regulating metabolism. It expected become new target for treatment disorders. The effects dual agonists on also provide more complete plan diseases. This article reviews research progress

Язык: Английский

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Reversal of High Fat Diet-Induced Obesity, Systemic Inflammation, and Astrogliosis by the NLRP3 Inflammasome Inhibitors NT-0249 and NT-0796

Journal of Pharmacology and Experimental Therapeutics, Год журнала: 2024, Номер 388(3), С. 813 - 826

Опубликована: Фев. 9, 2024

Systemic and cerebral inflammatory responses are implicated in the pathogenesis of obesity associated metabolic impairment. While NOD-, LRR-, pyrin domain-containing protein 3 (NLRP3) inflammasome has been linked to obesity-associated inflammation, whether it contributes development or maintenance is unknown. We provide support for a direct role saturated fatty acids, such as palmitic acid, NLRP3 activating stimuli obese states. To investigate activation diet-induced (DIO) mice, we tested two different clinical-stage inhibitors. demonstrate contributory this key established systemic inflammation. By comparing their effects calorie restriction, aimed identify specific NLRP3-sensitive mechanisms contributing obesity-induced inflammation (as opposed be those regulated by weight loss per se). In addition, comparison an inhibitor glucagon like peptide-1 receptor agonist, semaglutide (Wegovy), DIO model allowed appreciation relative efficacy these therapeutic strategies on obesity, its response, gliosis. show that structurally distinct, inhibitors, NT-0249 NT-0796, reverse mouse brain exposure appears necessary efficacy. this, DIO-driven hypothalamic glial fibrillary acidic expression blocked dosing with NT-0249/NT-0796. matching driven remarkably, inhibition provided enhanced improvements disease-relevant biomarkers acute phase cardiovascular lipid metabolism.

SIGNIFICANCE STATEMENT

Obesity global health concern predisposes individuals chronic disease diabetes at least part promoting report mice fed high-fat, obesogenic diet, reversed either inhibitors intracellular mediator NLRP3. Furthermore, reduces both gliosis circulating risk beyond what can achieved agonist restriction alone.

Язык: Английский

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Integrated Management of Cardiovascular–Renal–Hepatic–Metabolic Syndrome: Expanding Roles of SGLT2is, GLP-1RAs, and GIP/GLP-1-RAs

Biomedicines, Год журнала: 2025, Номер 13(1), С. 135 - 135

Опубликована: Янв. 8, 2025

Cardiovascular-Kidney-Metabolic syndrome, introduced by the American Heart Association in 2023, represents a complex and interconnected spectrum of diseases driven shared pathophysiological mechanisms. However, this framework notably excludes liver-an organ fundamental to metabolic regulation. Building on concept, Cardiovascular-Renal-Hepatic-Metabolic (CRHM) syndrome incorporates liver's pivotal role disease spectrum, particularly through its involvement via dysfunction-associated steatotic liver (MASLD). Despite increasing prevalence CRHM unified management strategies remain insufficiently explored. This review addresses following critical question: How can novel anti-diabetic agents, including sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), dual gastric inhibitory polypeptide (GIP)/GLP-1RA, offer an integrated approach managing beyond boundaries traditional specialties? By synthesizing evidence from landmark clinical trials, we highlight paradigm-shifting potential these therapies. SGLT2is, such as dapagliflozin empagliflozin, have emerged cornerstone guideline-directed treatments for heart failure (HF) chronic kidney (CKD), providing benefits that extend glycemic control are independent diabetes status. GLP-1RAs, e.g., semaglutide, transformed obesity enabling weight reductions exceeding 15% improving outcomes atherosclerotic cardiovascular (ASCVD), diabetic CKD, HF, MASLD. Additionally, tirzepatide, GIP/GLP-1RA, enables unprecedented loss (>20%), reduces risk over 90%, improves HF with preserved ejection fraction (HFpEF), MASLD, obstructive sleep apnea. moving organ-specific approach, propose integrates agents into holistic syndrome. paradigm shift moves away fragmented, organ-centric toward more fostering collaboration across specialties marking progress precision cardiometabolic medicine.

Язык: Английский

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Brain-wide cell-type-specific transcriptomic signatures of healthy ageing in mice

Nature, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Biological ageing can be defined as a gradual loss of homeostasis across various aspects molecular and cellular function1,2. Mammalian brains consist thousands cell types3, which may differentially susceptible or resilient to ageing. Here we present comprehensive single-cell RNA sequencing dataset containing roughly 1.2 million high-quality transcriptomes brain cells from young adult aged mice both sexes, regions spanning the forebrain, midbrain hindbrain. High-resolution clustering all results in 847 clusters reveals at least 14 age-biased that are mostly glial types. At broader subclass supertype levels, find age-associated gene expression signatures provide list 2,449 unique expressed genes (age-DE genes) for many neuronal non-neuronal Whereas most age-DE specific types, observe common with including decrease related structure function neuron major astrocyte types mature oligodendrocytes, an increase immune function, antigen presentation, inflammation, motility some vascular Finally, demonstrate greatest sensitivity concentrated around third ventricle hypothalamus, tanycytes, ependymal cells, certain arcuate nucleus, dorsomedial nucleus paraventricular express canonically energy homeostasis. Many these response. These findings suggest hypothalamus hub mouse brain. Overall, this study systematically delineates dynamic landscape cell-type-specific transcriptomic changes associated normal will serve foundation investigation functional interaction disease. A inform into

Язык: Английский

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The Effect of Semaglutide and GLP-1 RAs on Risk of Non-Arteritic Anterior Ischemic Optic Neuropathy

American Journal of Ophthalmology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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Mechanisms coupling the mTOR pathway to chronic obstructive pulmonary disease (COPD) pathogenesis

Cytokine & Growth Factor Reviews, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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