Liraglutide promotes the angiogenic ability of human umbilical vein endothelial cells through the JAK2/STAT3 signaling pathway.

Liraglutide promotes the angiogenic ability of human umbilical vein endothelial cells through the JAK2/STAT3 signaling pathway. Biochem Biophys Res Commun. 2020 Jan 13;: Authors: Di Y, He J, Ma P, Shen N, Niu C, Liu X, Du X, Tian F, Li H, Liu Y Abstract Liraglutide is a glucagon-like peptide-1 receptor (GLP-1R) agonist and incretin mimetic used for the treatment of Type 2 diabetes mellitus. It has also been shown to have a beneficial role in the cardiovascular system. Here, we investigated the mechanism by which liraglutide promotes angiogenesis using human umbilical vein endothelial cells (HUVECs). HUVECs were treated with various concentrations of liraglutide, and assessed by wound healing assay and tube formation assay as measures of angiogenesis. We found that liraglutide at 10 and 100 nmol/L greatly promoted the angiogenic ability of HUVECs. Next, we examined the JAK2/STAT3 signaling pathway and found that liraglutide treatment led to JAK2/STAT3 activation and significant increase in the angiogenic mediator expressions, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and endothelial nitric oxide synthase (eNOS) in HUVECs. Treatment with JAK2 inhibitor, AG490, in HUVECs successfully reduced the observed effects of liraglutide. We conclude that liraglutide promotes the angiogenic ability of HUVECs by activating the JAK2/STAT3 signaling pathway and upregulating its downstream factors, VEGF, bFGF and eNOS...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research

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Publication date: Available online 14 February 2020Source: Pharmacology &TherapeuticsAuthor(s): Shiying Shao, QinQin Xu, Xuefeng Yu, Ruping Pan, Yong ChenAbstractDipeptidyl peptidase 4 (DPP4) inhibitors (DPP4is) are oral anti-diabetic drugs (OADs) for the treatment of type 2 diabetes mellitus (T2DM) through inhibiting the degradation of incretin peptides. Numerous investigations have been focused on the effects of DPP4is on glucose homeostasis. However, there are limited evidences demonstrating their Potential modulatory functions in the immune system. DPP4, originally known as the lymphocyte cell surface protein CD26,...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research
Purpose of review Among the gastrointestinal hormones, the incretins: glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 have attracted interest because of their importance for the development and therapy of type 2 diabetes and obesity. New agonists and formulations of particularly the GLP-1 receptor have been developed recently showing great therapeutic efficacy for both diseases. Recent findings The status of the currently available GLP-1 receptor agonists (GLP-1RAs) is described, and their strengths and weaknesses analyzed. Their ability to also reduce cardiovascular and renal risk is describe...
Source: Current Opinion in Endocrinology, Diabetes and Obesity - Category: Endocrinology Tags: GASTROINTESTINAL HORMONES: Edited by H. Christian Weber Source Type: research
Publication date: Available online 24 September 2019Source: Canadian Journal of DiabetesAuthor(s): Abhinav Sharma, Subodh VermaAbstractThe growing global burden of type 2 diabetes mellitus confers significant morbidity and mortality in addition to significant cost to local health-care systems. In recent years, 2 classes of therapies have shown some promise in reducing the risk of adverse cardiovascular (CV) events: 1) glucagon-like-peptide-1 (GLP-1) receptor agonists and 2) sodium-glucose cotransporter-2 (SGLT-2) inhibitors. The mechanisms whereby these therapies reduce the risk of adverse CV outcomes are emerging. Both cl...
Source: Canadian Journal of Diabetes - Category: Endocrinology Source Type: research
ConclusionsRepeated administration of DR1060 provides potent and sustained glycemic control and body weight loss effect in high-fat DIO mice. DR10601 is a promising long-acting agent deserving further investigation for the treatment of type 2 diabetes and obesity.
Source: Journal of Endocrinological Investigation - Category: Endocrinology Source Type: research
Obesity and related metabolic disorders, including type 2 diabetes mellitus (T2DM), alarmingly grow up in the modern society thus representing a serious issue for endocrinology and medicine. Obesity is the major risk factor for T2DM [1], however, not all obese individuals ultimately develop T2DM. Nevertheless, mechanisms linking obesity to T2DM are being extensively studied.
Source: Diabetes Research and Clinical Practice - Category: Endocrinology Authors: Source Type: research
In this study we evaluated if the intake of an oleuropein-enriched chocolate could have positive effects on glycaemia and insulin levels in patients with type 2 diabetes mellitus (T2DM) and healthy subjects (HS).
Source: Clinical Nutrition - Category: Nutrition Authors: Tags: Original article Source Type: research
In this study, the predicted compounds were suggested as potent anti-diabetic candidates. Chosen structures were applied following computational strategies: The generation of the three-dimensional quantitative structure-activity relationship (3D QSAR) pharmacophore models, virtual screening, molecular docking, and de novo Evolution. The method also validated by performing re-docking and cross-docking studies of seven protein systems for which crystal structures were available for all bound ligands. The molecular docking experiments of predicted compounds within the binding pocket of DPP-IV were conducted. By using 25 train...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Publication date: Available online 23 July 2019Source: Nutrition, Metabolism and Cardiovascular DiseasesAuthor(s): Barchetta I, Ciccarelli G, Barone E, Cimini FA, Ceccarelli V, Bertoccini L, Sentinelli F, Tramutola A, Del Ben M, Angelico F, Baroni MG, Lenzi A, Cavallo MGAbstractBackgroundDipeptidyl peptidase 4 (DPP4) is a key enzyme involved in the regulation of the incretin system exerted by cleaving the glucagon-like peptide 1 (GLP-1); the blockage of DPP4, exerted by the antidiabetic agents DPP4-inhibitors (DPP4-I), results in greater GLP-1 concentration and improved glycaemic control. DPP4 acts also as a pro-inflammato...
Source: Nutrition, Metabolism and Cardiovascular Diseases - Category: Nutrition Source Type: research
CONCLUSION: While dietary fiber did not induce additional changes in glycemic parameters, it showed a trend of improvement in insulin sensitivity in 'responders.' Even if patients are already receiving diabetes treatment, the additional administration of fiber can lead to additional benefits in the treatment of diabetes. PMID: 31237126 [PubMed - as supplied by publisher]
Source: Diabetes and Metabolism Journal - Category: Endocrinology Tags: Diabetes Metab J Source Type: research
ConclusionsThis meta-analysis demonstrated that GLP-1RAs were associated with a significant reduction in major adverse CV events, CV death, stroke and death from any cause, while DPP-4 inhibitors were comparable to placebo for all CV outcomes, including hospitalizations for heart failure.RésuméObjectifsLes auteurs de deux grands essais randomisés ont récemment publié leurs conclusions concernant les effets d'un agoniste du récepteur au glucagon-like peptide-1 (A-GLP-1R) (essai HARMONY) et d'un inhibiteur de la dipeptidyl peptidase 4 (DPP-4) (essai CARMELINA) sur les b&eac...
Source: Canadian Journal of Diabetes - Category: Endocrinology Source Type: research
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