Comparative Transcriptome Analysis Reveals That Exendin-4 Improves Steatosis in HepG2 Cells by Modulating Signaling Pathways Related to Lipid Metabolism

Article Multidisciplinary Sciences

Exendin-4 alleviates steatosis in an in vitro cell model by lowering FABP1 and FOXA1 expression via the Wnt/-catenin signaling pathway

Olfa Khalifa et al.

Summary: Non-alcoholic fatty liver disease (NAFLD) is a leading chronic liver disease worldwide, and glucagon-like peptide-1 receptor (GLP-1R) agonists can reduce NAFLD by decreasing fatty acid uptake and transport.

SCIENTIFIC REPORTS (2022)

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Review Endocrinology & Metabolism

The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists for the Management of NAFLD

Chandani Patel Chavez et al.

Summary: The burden of cirrhosis from nonalcoholic fatty liver disease (NAFLD) is becoming widespread in the United States. There needs to be greater awareness among endocrinologists, who often see but may miss the diagnosis in adults with obesity or type 2 diabetes mellitus (T2D) who are at high risk. Recent studies suggest that glucagon-like peptide-1 receptor agonists (GLP-1RAs) have beneficial effects on nonalcoholic steatohepatitis (NASH) in this population.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2022)

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Article Gastroenterology & Hepatology

Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial

Anat Yaskolka Meir et al.

Summary: The study found that a green-Mediterranean diet (MED) is more effective in reducing non-alcoholic fatty liver disease (NAFLD), with a greater decrease in intrahepatic fat (IHF) content, by further restricting red/processed meat and increasing intake of green plants and polyphenols. This healthy dietary strategy shows promising results in reducing IHF and decreasing NAFLD prevalence.

GUT (2021)

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Review Gastroenterology & Hepatology

A review of non-alcoholic fatty liver disease in non-obese and lean individuals

Mitra Ahadi et al.

Summary: Non-alcoholic fatty liver disease (NAFLD) is a common cause of liver disorders associated with type 2 diabetes mellitus, dyslipidemia, metabolic syndrome, and obesity. The pathogenesis of NAFLD in non-obese patients involves genetic predispositions and dietary factors, particularly high fructose consumption. Treatment typically involves lifestyle changes such as dietary modification, weight loss, and increased physical activity.

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY (2021)

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Article Biochemistry & Molecular Biology

Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials

Alessandro Mantovani et al.

Summary: Treatment with GLP-1 RAs, particularly liraglutide and semaglutide, shows promising results in reducing liver fat content, serum liver enzyme levels, and improving histological resolution of NASH without worsening liver fibrosis in patients with NAFLD or NASH. Further investigations are warranted.

METABOLITES (2021)

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Article Endocrinology & Metabolism

Diet and exercise reduce pre-existing NASH and fibrosis and have additional beneficial effects on the vasculature, adipose tissue and skeletal muscle via organ-crosstalk

Anita M. van den Hoek et al.

Summary: Exercise, dietary change, and their combination can reverse established NASH/fibrosis in obese Ldlr-/-.Leiden mice, with beneficial effects on atherosclerosis, WAT inflammation, and muscle function. Exercise and dietary change affect distinct pathways related to steatosis and lipid metabolism, acting complementarily when combined, resulting in an additive effect on important endpoints including NASH and atherosclerosis. For inflammation, exercise and diet share several pathways, leading to a similar net effect when interventions are combined.

METABOLISM-CLINICAL AND EXPERIMENTAL (2021)

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Review Medicine, Research & Experimental

Weight Loss and Maintenance Related to the Mechanism of Action of Glucagon-Like Peptide 1 Receptor Agonists

Jamy Ard et al.

Summary: Obesity is a chronic disease with many complications, and weight loss can help improve related health issues. However, there are challenges in accessing and using anti-obesity medications, which can assist in achieving and maintaining weight loss. Addressing barriers to medication use can help in the long-term management of obesity and reducing associated risks.

ADVANCES IN THERAPY (2021)

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Article Medicine, General & Internal

A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis

Philip N. Newsome et al.

Summary: This phase 2 trial demonstrated that treatment with semaglutide resulted in a significantly higher percentage of patients with NASH resolution compared to placebo in patients with NASH, but did not show a significant between-group difference in the percentage of patients with an improvement in fibrosis stage.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Review Endocrinology & Metabolism

Glucagon-Like Peptide-1 Receptor Agonists for Non-Alcoholic Fatty Liver Disease in Type 2 Diabetes: A Meta-Analysis

Chloe Wong et al.

Summary: This meta-analysis examined the efficacy of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus. Results showed significant improvements in hepatic fat content, liver biochemistry, body composition, glucose parameters, lipid parameters, insulin sensitivity, and inflammatory markers following treatment with glucagon-like peptide-1 receptor agonists. Glucagon-like peptide-1 receptor agonists were also found to significantly decrease hepatic fat content compared to other treatments, showing promise in improving both diabetes and non-alcoholic fatty liver disease phenotype.

FRONTIERS IN ENDOCRINOLOGY (2021)

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Article Endocrinology & Metabolism

Efficacy of Weight Reduction on Pediatric Nonalcoholic Fatty Liver Disease: Opportunities to Improve Treatment Outcomes Through Pharmacotherapy

Chance S. Friesen et al.

Summary: Obesity is the main risk factor for nonalcoholic fatty liver disease in children, making early, effective weight loss intervention crucial for disease prevention. Pharmacotherapy is becoming an increasingly important option for weight reduction and NAFLD management in children, especially in settings where lifestyle modifications are not successful.

FRONTIERS IN ENDOCRINOLOGY (2021)

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Review Gastroenterology & Hepatology

Non-alcoholic fatty liver disease: a multisystem disease requiring a multidisciplinary and holistic approach

Giovanni Targher et al.

Summary: NAFLD is not only a global public health issue but also proven to be a systemic disease, closely related to various extrahepatic complications. Addressing NAFLD requires establishing a multidisciplinary working group and framework to achieve comprehensive, person-centered care and management.

LANCET GASTROENTEROLOGY & HEPATOLOGY (2021)

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Review Biochemistry & Molecular Biology

FXR in liver physiology: Multiple faces to regulate liver metabolism

Katrin Panzitt et al.

Summary: The liver serves as a central metabolic hub that coordinates nutritional inputs and metabolic outputs. FXR in the liver and intestine plays a crucial role in regulating postprandial nutrient disposal. Aside from classical roles, FXR also has effects on amino acid, protein metabolism, autophagic turnover, and inflammation, which are less studied. Additionally, understanding of how FXR signaling is affected by posttranslational modifications and different isoforms is important for potential pharmaceutical targeting in clinical applications.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE (2021)

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Article Medicine, Research & Experimental

Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4

Khaoula Errafii et al.

Summary: This study confirmed that Ex-4 can improve steatosis in HepG2 cells and identified 379 and 180 differentially expressed LncRNAs between untreated, steatotic, and Ex-4-treated steatotic cells. Functional enrichment analysis revealed critical pathways involved in fatty acid and pyruvate metabolism, insulin, PPAR, Wnt, TGF-beta, mTOR, VEGF, NOD-like, and Toll-like receptors signaling pathways.

JOURNAL OF TRANSLATIONAL MEDICINE (2021)

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Article Multidisciplinary Sciences

Body weight gain rather than body weight variability associated with increased risk of nonalcoholic fatty liver disease

Eun Ju Cho et al.

Summary: This study found that weight gain, rather than variability, is independently associated with the risk of incident NAFLD. Individuals with weight gain >= 10% and 7%-10% had significantly higher risk of incident NAFLD, while those with -7%--3% had significantly lower risk. Understanding this association may have future clinical implications for the treatment of NAFLD patients through quantifying weight loss.

SCIENTIFIC REPORTS (2021)

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Article Cell Biology

Epigenetic Regulation of Peroxisome Proliferator-Activated Receptor Gamma Mediates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease

Tahar Hajri et al.

Summary: The study demonstrated that high-fat diet and palmitic acid overload increased the expression of PPAR gamma and its target genes through epigenetic mechanisms, leading to enhanced fatty acid uptake and storage, and excess hepatic lipid accumulation. This highlights the crucial role of epigenetic regulation in the pathogenesis of NAFLD.

CELLS (2021)

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Review Gastroenterology & Hepatology

The Prevalence of Lean/Nonobese Nonalcoholic Fatty Liver Disease A Systematic Review and Meta-Analysis

Yiwen Shi et al.

JOURNAL OF CLINICAL GASTROENTEROLOGY (2020)

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Article Endocrinology & Metabolism

Current and emerging pharmacological options for the treatment of nonalcoholic steatohepatitis

Stergios A. Polyzos et al.

METABOLISM-CLINICAL AND EXPERIMENTAL (2020)

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Article Biochemistry & Molecular Biology

Hepatocyte-specific Nrf2 deficiency mitigates high-fat diet-induced hepatic steatosis: Involvement of reduced PPARγ expression

Lu Li et al.

REDOX BIOLOGY (2020)

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Article Endocrinology & Metabolism

Role of ATP-binding cassette transporter A1 in suppressing lipid accumulation by glucagon-like peptide-1 agonist in hepatocytes

Jingya Lyu et al.

MOLECULAR METABOLISM (2020)

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Review Nutrition & Dietetics

Effects of Dietary and Lifestyle Interventions on Liver, Clinical and Metabolic Parameters in Children and Adolescents with Non-Alcoholic Fatty Liver Disease: A Systematic Review

Christina N. Katsagoni et al.

NUTRIENTS (2020)

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Article Gastroenterology & Hepatology

Spatial expression of glucagon-like peptide 1 receptor and caveolin-1 in hepatocytes with macrovesicular steatosis in non-alcoholic steatohepatitis

Hiroaki Yokomori et al.

BMJ OPEN GASTROENTEROLOGY (2020)

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Review Gastroenterology & Hepatology

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

Areti Sofogianni et al.

WORLD JOURNAL OF HEPATOLOGY (2020)

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Review Gastroenterology & Hepatology

The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis

Zobair M. Younossi et al.

JOURNAL OF HEPATOLOGY (2019)

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Review Gastroenterology & Hepatology

Biomarkers and subtypes of deranged lipid metabolism in non-alcoholic fatty liver disease

Jose M. Mato et al.

WORLD JOURNAL OF GASTROENTEROLOGY (2019)

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Article Gastroenterology & Hepatology

Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development

Juliette Mouries et al.

JOURNAL OF HEPATOLOGY (2019)

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Article Multidisciplinary Sciences

Multi-technique comparison of atherogenic and MCD NASH models highlights changes in sphingolipid metabolism

Sophie A. Montandon et al.

SCIENTIFIC REPORTS (2019)

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Review Gastroenterology & Hepatology

Non-alcoholic fatty liver disease in lean individuals

Somaya Albhaisi et al.

JHEP REPORTS (2019)

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Review Biochemistry & Molecular Biology

Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease

David Hojland Ipsen et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2018)

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Review Gastroenterology & Hepatology

Non-alcoholic fatty liver disease and hypertension: coprevalent or correlated?

Dimitrios Oikonomou et al.

EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY (2018)

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Review Gastroenterology & Hepatology

Current and future therapeutic regimens for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Zobair M. Younossi et al.

HEPATOLOGY (2018)

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Article Endocrinology & Metabolism

Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR

Kavita Jadhav et al.

MOLECULAR METABOLISM (2018)

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Review Endocrinology & Metabolism

Pleiotropic Effects of GLP-1 and Analogs on Cell Signaling, Metabolism, and Function

Jordan Rowlands et al.

FRONTIERS IN ENDOCRINOLOGY (2018)

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Review Biochemistry & Molecular Biology

Liver X receptors link lipid metabolism and inflammation

Ira G. Schulman

FEBS LETTERS (2017)

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Article Gastroenterology & Hepatology

Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases

Leon A. Adams et al.

GUT (2017)

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Article Biochemistry & Molecular Biology

A Novel Interacting Protein SERP1 Regulates the N-Linked Glycosylation and Function of GLP-1 Receptor in the Liver

Yuanyuan Xiao et al.

JOURNAL OF CELLULAR BIOCHEMISTRY (2017)

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Article Gastroenterology & Hepatology

Treatment of NAFLD with diet, physical activity and exercise

Manuel Romero-Gómez et al.

JOURNAL OF HEPATOLOGY (2017)

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Review Pediatrics

Insulin Resistance and NAFLD: A Dangerous Liaison beyond the Genetics

Melania Manco

CHILDREN-BASEL (2017)

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Article Biochemistry & Molecular Biology

Antiobesity efficacy of GLP-1 receptor agonist liraglutide is associated with peripheral tissue-specific modulation of lipid metabolic regulators

Juan Decara et al.

BIOFACTORS (2016)

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Article Endocrinology & Metabolism

Hepatocyte-Specific Disruption of CD36 Attenuates Fatty Liver and Improves Insulin Sensitivity in HFD-Fed Mice

Camella G. Wilson et al.

ENDOCRINOLOGY (2016)

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Article Medicine, Research & Experimental

Low simvastatin concentrations reduce oleic acid-induced steatosis in HepG2 cells: An in vitro model of non-alcoholic fatty liver disease

Mohammad J. Alkhatatbeh et al.

EXPERIMENTAL AND THERAPEUTIC MEDICINE (2016)

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Article Multidisciplinary Sciences

Exendin-4 Inhibits Hepatic Lipogenesis by Increasing β-Catenin Signaling

Mi Hae Seo et al.

PLOS ONE (2016)

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Article Pathology

PPARα-Deficient ob/ob Obese Mice Become More Obese and Manifest Severe Hepatic Steatosis Due to Decreased Fatty Acid Oxidation

Qian Gao et al.

AMERICAN JOURNAL OF PATHOLOGY (2015)

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Review Gastroenterology & Hepatology

Bile acid activated receptors are targets for regulation of integrity of gastrointestinal mucosa

Eleonora Distrutti et al.

JOURNAL OF GASTROENTEROLOGY (2015)

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Article Gastroenterology & Hepatology

Central obesity and nonalcoholic fatty liver disease risk after adjusting for body mass index

Qing Pang et al.

WORLD JOURNAL OF GASTROENTEROLOGY (2015)

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Article Biology

LXRs link metabolism to inflammation through Abca1-dependent regulation of membrane composition and TLR signaling

Ayaka Ito et al.

ELIFE (2015)

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Review Chemistry, Multidisciplinary

Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis

Yang Jiao et al.

ACTA PHARMACOLOGICA SINICA (2015)

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Article Chemistry, Multidisciplinary

Synthetic FXR Agonist GW4064 Prevents Diet-Induced Hepatic Steatosis and Insulin Resistance

Yongjie Ma et al.

PHARMACEUTICAL RESEARCH (2013)

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Review Gastroenterology & Hepatology

Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis

Seung-Hoi Koo

CLINICAL AND MOLECULAR HEPATOLOGY (2013)

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Article Gastroenterology & Hepatology

Activation of Liver X Receptors Attenuates Endotoxin-Induced Liver Injury in Mice with Nonalcoholic Fatty Liver Disease

Yuan Liu et al.

DIGESTIVE DISEASES AND SCIENCES (2012)

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Article Medicine, Research & Experimental

Enhanced expression of pro-inflammatory mediators and liver X-receptor-regulated lipogenic genes in non-alcoholic fatty liver disease and hepatitis C

Elena Lima-Cabello et al.

CLINICAL SCIENCE (2011)

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Article Endocrinology & Metabolism

Up-Regulation of PPAR-γ mRNA Expression in the Liver of Obese Patients: an Additional Reinforcing Lipogenic Mechanism to SREBP-1c Induction

Paulina Pettinelli et al.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2011)

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Article Gastroenterology & Hepatology

Glucagon-like peptide-1 receptor activation stimulates hepatic lipid oxidation and restores hepatic signalling alteration induced bya high-fat diet in nonalcoholic steatohepatitis

Gianluca Svegliati-Baroni et al.

LIVER INTERNATIONAL (2011)

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Article Biochemistry & Molecular Biology

Intrahepatic cholesterol influences progression, inhibition and reversal of non-alcoholic steatohepatitis in hyperlipidemic mice

Kristiaan Wouters et al.

FEBS LETTERS (2010)

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Article Gastroenterology & Hepatology

Glucagon-Like Peptide-1 Receptor Is Present on Human Hepatocytes and Has a Direct Role in Decreasing Hepatic Steatosis In Vitro by Modulating Elements of the Insulin Signaling Pathway

Nitika Arora Gupta et al.

HEPATOLOGY (2010)

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Article Endocrinology & Metabolism

Endogenous Glucagon-Like Peptide-1 Slows Gastric Emptying in Healthy Subjects, Attenuating Postprandial Glycemia

Adam M. Deane et al.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2010)

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Article Endocrinology & Metabolism

Increased hepatic CD36 expression contributes to dyslipidemia associated with diet-induced obesity

Debby P. Y. Koonen et al.

DIABETES (2007)

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Review Medicine, General & Internal

The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes

Daniel J. Drucker et al.

LANCET (2006)

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Review Medicine, Research & Experimental

Liver X receptors as integrators of metabolic and inflammatory signaling

N Zelcer et al.

JOURNAL OF CLINICAL INVESTIGATION (2006)

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Article Gastroenterology & Hepatology

Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice

XK Ding et al.

HEPATOLOGY (2006)

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Article Endocrinology & Metabolism

Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects

T Vilsboll et al.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2003)

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Article Endocrinology & Metabolism

Glucagon-like peptide-1 infusion must be maintained for 24 h/day to obtain acceptable glycemia in type 2 diabetic patients who are poorly controlled on sulphonylurea treatment

J Larsen et al.

DIABETES CARE (2001)

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Review Gastroenterology & Hepatology

Peroxisomal beta-oxidation and steatohepatitis

MS Rao et al.

SEMINARS IN LIVER DISEASE (2001)

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Comparative Transcriptome Analysis Reveals That Exendin-4 Improves Steatosis in HepG2 Cells by Modulating Signaling Pathways Related to Lipid Metabolism

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