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glucagon-like peptide-1 receptor agonists:Exploring the mechanisms from glycemic control to treatment of multisystemic diseases

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World Journal of Gastroenterology 2024年第36期30卷 4036-4043页

作者： Mo-Wei Kong Yang Yu Ying Wan Yu Gao Chun-Xiang Zhang Department of Cardiology Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina School of Basic Medical Sciences Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Department of Endocrinology The Affiliated Hospital of Chengde Medical CollegeChengde 067000Hebei ProvinceChina Department of Cardiology The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Key Laboratory of Medical Electrophysiology Ministry of EducationInstitute of Cardiovascular ResearchBasic Medicine Research Innovation Center for Cardiometabolic DiseasesMinistry of EducationNucleic Acid Medicine of Luzhou Key LaboratorySouthwest Medical UniversityLuzhou 646000Sichuan ProvinceChina

This editorial takes a deeper look at the insights provided by Soresi and Giannitrapani,which examined the therapeutic potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)for metabolic dysfunction-associated fatty liver *** provide supplementary insights to their research,highlighting the broader systemic implications of GLP-1RAs,synthesizing the current understanding of their mechanisms and the trajectory of research in this ***-1RAs are revolutionizing the treatment of type 2 diabetes mellitus and *** glycemic control,GLP-1RAs demonstrate cardiovascular and renal protective effects,offering potential in managing diabetic kidney disease alongside renin–angiotensin–aldosterone system *** role in bone metabolism hints at benefits for diabetic osteoporosis,while the neuroprotective properties of GLP-1RAs show promise in Alzheimer's disease treatment by modulating neuronal insulin ***,they improve hormonal and metabolic profiles in polycystic ovary *** editorial highlights the multifaceted mechanisms of GLP-1RAs,emphasizing the need for ongoing research to fully realize their therapeutic potential across a range of multisystemic diseases.

关键词： glucagon-like peptide-1 receptor agonists Glycemic control Multisystem diseases Mechanism of action Cardiovascular protection Renal disease Bone metabolism Non-alcoholic fatty liver disease Neuroprotection Polycystic ovary syndrome

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glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: An update

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World Journal of Hepatology 2020年第8期12卷 493-505页

作者： Areti Sofogianni Athanasios Filippidis Lampros Chrysavgis Konstantinos Tziomalos Evangelos Cholongitas First Propedeutic Department of Internal Medicine Medical SchoolAristotle University of ThessalonikiAHEPA HospitalThessaloniki 54636Greece First Department of Internal Medicine Laiko General HospitalMedical School of National and Kapodistrian University of AthensAthens 11527Greece

Non-alcoholic fatty liver disease(NAFLD)is the predominant cause of chronic liver disease *** progresses in some cases to non-alcoholic steatohepatitis(NASH),which is characterized,in addition to liver fat deposition,by hepatocyte ballooning,inflammation and liver fibrosis,and in some cases may lead to hepatocellular *** prevalence increases along with the rising incidence of type 2 diabetes mellitus(T2DM).Currently,lifestyle interventions and weight loss are used as the major therapeutic strategy in the vast majority of patients with ***-like peptide-1 receptor agonists(GLP-1RAs)are used in the management of T2DM and do not have major side effects like *** patients with NAFLD,the GLP-1 receptor production is ***,several animal and human studies have emphasized the role of GLP-1RAs in ameliorating liver fat accumulation,alleviating the inflammatory environment and preventing NAFLD progression to *** this review,we summarize the updated literature data on the beneficial effects of GLP-1RAs in NAFLD/***,as GLP-1RAs seem to be an attractive therapeutic option for T2DM patients with concomitant NAFLD,we discuss whether GLP-1RAs should represent the first line pharmacotherapy for these patients.

关键词： glucagon-like peptide-1 receptor agonists Non-alcoholic fatty liver disease Type 2 diabetes mellitus Clinical studies Fatty liver Animal studies

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glucagon-like peptide-1 receptor agonists as a possible intervention to delay the onset of type 1 diabetes:A new horizon

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World Journal of Diabetes 2024年第2期15卷 133-136页

作者： Mahmoud Nassar Ajay Chaudhuri Husam Ghanim Paresh Dandona Department of Internal Medicine Division of EndocrinologyDiabetes and MetabolismJacobs School of Medicine and Biomedical SciencesUniversity of BuffaloBuffaloNY 14221United States

Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and *** management of T1D primarily focuses on exogenous insulin replacement to control blood glucose ***,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta *** research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of ***-1RAs are medications initially developed for treating type 2 *** exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric *** evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with *** article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of *** article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.

关键词： Type 1 diabetes Semaglutide glucagon-like peptide-1 receptor agonists Insulin therapy Autoimmune response Blood glucose monitoring Β-cell preservation Early screening Teplizumab Randomized controlled trials

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Effects of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease and inflammation

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World Journal of Gastroenterology 2014年第40期20卷 14821-14830页

作者： Xing-Chun Wang Aaron M Gusdon Huan Liu Shen Qu Department of Endocrinology and Metabolism Shanghai 10th People’s Hospital Tongji University Nanjing Medical University Department of Neurology and Neuroscience Weill Cornell Medical College New York NY 10065 United States

glucagon-like peptide1 (GLP-1) is secreted from Langerhans cells in response to oral nutrient intake. glucagon- like peptide-1 receptor agonists (GLP-1RAs) are a new class of incretin-based anti-diabetic drugs. They function to stimulate insulin secretion while suppressing glucagon secretion. GLP-1-based therapies are now well established in the management of type 2 diabetes mellitus (T2DM), and recent literature has suggested potential applications of these drugs in the treatment of obesity and for protection against cardiovascular and neurological diseases. As we know, along with change in lifestyles, the prevalence of non-alcoholic fatty liver disease (NAFLD) in China is rising more than that of viral hepatitis and alcoholic fatty liver disease, and NAFLD has become the most common chronic liver disease in recent years. Recent studies further suggest that GLP-1RAs can reduce transaminase levels to improve NAFLD by improving blood lipid levels, cutting down the fat content to promote fat redistribution, directly decreasing fatty degeneration of the liver, reducing the degree of liver fibrosis and improving inflammation. This review shows the NAFLD-associated effects of GLP-1RAs in animal models and in patients with T2DM or obesity who are participants in clinical trials. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

关键词： glucagon-like peptide-1 receptor agonists Liver function Fat content Non-alcoholic fatty liver disease Inflammation

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Effects of glucagon-like peptide-1 receptor agonists on glucose excursion and inflammation in overweight or obese type 2 diabetic patients

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World Journal of Diabetes 2023年第8期14卷 1280-1288页

作者： Xiao-Min Huang Xing Zhong Yi-Jun Du Yan-Yun Guo Tian-Rong Pan Department of Endocrinology The Second Affiliated Hospital of Anhui Medical UniversityHefei 230601Anhui ProvinceChina

BACKGROUND Currently,the lack of comparative studies between weekly and daily formulations of glucagon-like peptide-1 receptor agonists(GLP-1RAs)for glucose excursion is worth *** To investigate the effects of weekly and daily formulations of GLP-1RA on glucose excursion and inflammation in overweight and obese patients with type 2 *** Seventy patients with type 2 diabetes mellitus who were treated at our hospital between January 2019 and January 2022 were enrolled in this retrospective *** patients were treated with *** evaluated changes in blood glucose levels and a series of important indicators in patients before and after treatment with either a weekly or daily preparation of GLP-1RA(group A;n=33 and group B;n=37).RESULTS The degree of decrease in the levels of fasting blood glucose,mean blood glucose,mean amplitude of glycemic excursions,total cholesterol,triglycerides,tumor necrosis factor-α,interleukin-6,and high-sensitivity C-reactive protein after treatment in group A was higher than that in group B(P1).However,there were no statistically significant differences in the levels of glycated hemoglobin,standard deviation of blood glucose,coefficient of variation,absolute mean of daily differences,percentage of time with 3.9 mmol/L10 mmol/L,and high-and low-density lipoproteins between the two groups(P>0.05).The incidence of adverse reactions was significantly lower in group A than in group B(P1RA in controlling blood glucose levels in the patients,suppressing inflammation,and reducing adverse reactions was significantly higher than that of the daily preparations,which is worthy of clinical promotion.

关键词： glucagon-like peptide-1 receptor agonists Weekly preparation Daily preparation Overweight or obese Type 2 diabetes mellitus Glucose excursion Inflammation

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Is there a role for glucagon-like peptide-1 receptor agonists in the management of diabetic nephropathy?

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World Journal of Diabetes 2020年第9期11卷 370-373页

作者： Stavroula Veneti Konstantinos Tziomalos Department of Internal Medicine Medical SchoolAristotle University of ThessalonikiAHEPA HospitalThessaloniki 54636Greece

Chronic kidney disease constitutes a major microvascular complication of diabetes *** data suggest that glucagon-like peptide-1 receptor agonists(GLP-1 RAs)might have a role in the management of diabetic kidney disease(DKD).GLP-1 RAs appear to reduce the incidence of persistent macro-albuminuria in patients with type 2 diabetes *** beneficial effect appears to be mediated not only by the glucose-lowering action of these agents but also on their blood pressure lowering,anti-inflammatory and antioxidant *** the other hand,GLP-1 RAs do not appear to affect the rate of decline of glomerular filtration ***,this might be due to the relatively short duration of the trials that evaluated their effects on ***,these trials were not designed nor powered to assess renal *** than macrolbuminuria is a strong risk factor for the progression of DKD,it might be expected that GLP-1 RAs will prevent the deterioration in renal function in the long ***,this remains to be shown in appropriately designed randomized controlled trials in patients with DKD.

关键词： Diabetic nephropathy Type 2 diabetes mellitus glucagon-like peptide-1 receptor agonists Liraglutide Dulaglutide Semaglutide

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Review on the Effect of glucagon-like peptide-1 receptor agonists and Dipeptidyl Peptidase-4 Inhibitors for the Treatment of Non-Alcoholic Fatty Liver Disease

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2015年第3期35卷 333-336页

作者：李超林赵璐杰周新丽吴慧潇赵家军 Department of Endocrinology Shandong Provincial Hospital Affiliated to Shandong University Department of Endocrinology Yantai Yuhuangding Hospital Affiliated to Qingdao University Hemodialysis Center Yantai Yuhuangding Hospital Affiliated to Qingdao University

Non-alcoholic fatty liver disease（NAFLD） is a common liver disease and it represents the hepatic manifestation of metabolic syndrome, which includes type 2 diabetes mellitus（T2DM）, dyslipidemia, central obesity and hypertension. glucagon-like peptide-1（GLP-1） analogues and dipeptidyl peptidase-4（DPP-4） inhibitors were widely used to treat T2 DM. These agents improve glycemic control, promote weight loss and improve lipid metabolism. Recent studies have demonstrated that the GLP-1 receptor（GLP-1R） is present and functional in human and rat hepatocytes. In this review, we present data from animal researches and human clinical studies that showed GLP-1 analogues and DPP-4 inhibitors can decrease hepatic triglyceride（TG） content and improve hepatic steatosis, although some effects could be a result of improvements in metabolic parameters. Multiple hepatocyte signal transduction pathways and m RNA from key enzymes in fatty acid metabolism appear to be activated by GLP-1 and its analogues. Thus, the data support the need for more rigorous prospective clinical trials to further investigate the potential of incretin therapies to treat patients with NAFLD.

关键词： glucagon-like peptide-1 receptor agonists dipeptidyl peptidase-4 non-alcoholic fatty liverdisease insulin resistance type 2 diabetes mellitus

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Interplay of gut microbiota,glucagon-like peptide receptor agonists,and nutrition:New frontiers in metabolic dysfunction-associated steatotic liver disease therapy

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World Journal of Gastroenterology 2024年第43期30卷 4682-4688页

作者： Merve Guney-Coskun Metin Basaranoglu Department of Nutrition and Dietetics Faculty of Health SciencesIstanbul Medipol UniversityIstanbul 34810Türkiye Department of Nutrition and Dietetics Graduate School of HealthSciencesIstanbul Medipol UniversityIstanbul 34810Türkiye Department of Gastroenterology and Hepatology Faculty of MedicineBezmialem Vakif UniversityIstanbul 34093Türkiye

The gut-liver axis plays a crucial role in the development and progression of metabolic dysfunction-associated steatotic liver disease(MASLD).Key metabolites,including lipopolysaccharides,short-chain fatty acids(SCFAs),bile acids,and beneficial gut bacteria such as Bifidobacterium and Lactobacillus,are pivotal in this ***-like peptide-1 receptor agonists(GLP-1 RAs)show promise in managing MASLD by promoting weight loss,enhancing insulin secretion,and improving liver *** restore gut-liver axis functionality,and their effects are amplified through dietary modifications and gut microbiometargeted *** research highlights the interplay between GLP-1 RAs and gut microbiota,indicating that the gut microbiome significantly influences therapeutic *** produced by gut bacteria,can stimulate glucagon-like peptide-1(GLP-1)secretion,further improving metabolic *** dietary interventions with GLP-1 RA treatment may enhance liver health by modulating the gut microbiota-SCFAs-GLP-1 *** research is needed to understand personalized effects,with prebiotics and probiotics offering treatment avenues for MASLD.

关键词： Metabolic dysfunction-associated steatotic liver disease glucagon-like peptide-1 receptor agonists Gut microbiome Gut-liver axis Diet intervention

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glucagon-like peptide-1 agonists:Role of the gut in hypoglycemia unawareness,and the rationale in type 1 diabetes

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World Journal of Diabetes 2024年第11期15卷 2167-2172页

作者： Hyder O Mirghani Internal Medicine University of TabukTabuk 51941TabukSaudi Arabia

Type 1 diabetes is increasing and the majority of patients have poor glycemic *** advanced technology and nanoparticle use have greatly enhanced insulin delivery and glucose monitoring,weight gain and hypoglycemia remain major challenges and a constant source of concern for patients with type 1 *** 1 diabetes shares some pathophysiology with type 2 diabetes,and an overlap has been *** above observation created great interest in glucagon-like peptide-1 receptor agonists(GLP-1)as adjuvants for type 1 *** trials confirmed the positive influence of GLP-1 agonists onβcell ***,hypoglycemia unawareness and dysregulated glucagon response have been previously reported in patients with recurrent hypoglycemia using GLP-1 *** et al found that the source of glucagon dysregulation due to GLP-1 agonists resides in the *** explanations could be gut nervous system dysregulation or gut microbiota *** review evaluates the potential of GLP-1 agonists in managing type 1 diabetes,particularly focusing on their impact on glycemic control,weight management,and glucagon *** provide a broader insight into the problem of type 1 diabetes mellitus management in the light of recent findings and provide future research directions.

关键词： glucagon-like peptide-1 receptor agonists glucagon response Hypoglycemia unawareness Gut Type 1 diabetes

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GLP-1 receptor agonists and myocardial metabolism in atrial fibrillation

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Journal of Pharmaceutical Analysis 2024年第5期14卷 653-665页

作者： Jiani Zhong Hang Chen Qiming Liu Shenghua Zhou Zhenguo Liu Yichao Xiao Department of Cardiovascular Medicine Second Xiangya HospitalCentral South UniversityChangsha410011China Xiangya School of Medicine Central South UniversityChangsha410008China Center for Precision Medicine and Division of Cardiovascular Medicine Department of MedicineSchool of MedicineUniversity of MissouriColumbiaMO65211USA

Atrial fibrillation(AF)is the most common cardiac *** medical conditions,including hypertension,diabetes,obesity,sleep apnea,and heart failure(HF),increase the risk for *** have unique metabolic characteristics to maintain adenosine triphosphate *** changes occur in myocardial metabolism in ***-like peptide-1 receptor agonists(GLP-1RAs)have been used to control blood glucose fluctuations and weight in the treatment of type 2 diabetes mellitus(T2DM)and ***-1RAs have also been shown to reduce oxidative stress,inflammation,autonomic nervous system modulation,and mitochondrial *** article reviews the changes in metabolic characteristics in cardiomyocytes in *** the clinical trial outcomes are unsatisfactory,the findings demonstrate that GLP-1 RAs can improve myocardial metabolism in the presence of various risk factors,lowering the incidence of AF.

关键词： Atrial fibrillation glucagon-like peptide-1 receptor agonists Metabolism

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