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Exendin

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https://www.readbyqxmd.com/read/29226686/enhanced-specific-activity-by-multi-chelation-of-exendin-3-leads-to-improved-image-quality-and-in-vivo-beta-cell-imaging
#1
Lieke Joosten, Maarten Brom, Hanneke Peeters, Sandra Heskamp, Martin Behe, Otto C Boerman, Martin Gotthardt
OBJECTIVE: Glucagon like peptide-1 receptor (GLP-1R) targeting using radiolabeled exendin is a promising approach to non-invasively visualize and determine beta cell mass (BCM), which could help to unravel the pathophysiology of diabetes. However, saturation of the GLP-1R on beta cells occurs at low peptide doses, since the number of receptors expressed under physiological conditions is low. Therefore, tracers with high specific activities are required to sensitively image small variations in BCM...
December 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29226617/activation-of-glucagon-like-peptide-1-receptors-in-the-nucleus-accumbens-attenuates-cocaine-seeking-in-rats
#2
Nicole S Hernandez, Bernadette O'Donovan, Pavel I Ortinski, Heath D Schmidt
Recent evidence indicates that activation of glucagon-like peptide-1 (GLP-1) receptors reduces cocaine-mediated behaviors and cocaine-evoked dopamine release in the nucleus accumbens (NAc). However, no studies have examined the role of NAc GLP-1 receptors in the reinstatement of cocaine-seeking behavior, an animal model of relapse. Here, we show that systemic infusion of a behaviorally relevant dose of the GLP-1 receptor agonist exendin-4 penetrated the brain and localized with neurons and astrocytes in the NAc...
December 11, 2017: Addiction Biology
https://www.readbyqxmd.com/read/29225158/exendin-4-partly-ameliorates-of-hyperglycemia-mediated-tissue-damage-in-lungs-of-streptozotocin-induced-diabetic-mice
#3
Fusun Oztay, Serap Sancar Bas, Selda Gezginci-Oktayoglu, Merve Ercin, Sehnaz Bolkent
Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion, and plays anti-inflammatory role in atherosclerosis, and has surfactant-releasing effects in lungs. GLP-1 analogues are used in diabetes therapy. This is the first study to investigate the effects of exendin-4, a GLP-1 receptor agonist, on lung injury in diabetic mice. BALB/c male mice were divided into four groups. The first group was given only citrate buffer, the second group was given only exendin-4, the third group was given only streptozotocin (STZ), and the fourth group was given both exendin-4 and STZ...
December 7, 2017: Peptides
https://www.readbyqxmd.com/read/29223528/glp-1-receptor-agonists-downregulate-aberrant-gnt-iii-expression-in-alzheimer-s-disease-models-through-the-akt-gsk-3%C3%AE-%C3%AE-catenin-signaling
#4
Ying Wang, Song Chen, Zheng Xu, Suting Chen, Wenbing Yao, Xiangdong Gao
Alterations of glycoprotein glycans contribute to a wide variety of diseases. Bisecting N-acetylglucosamine (GlcNAc) levels increased in the cerebrospinal fluid of most Alzheimer's disease (AD) patients, and the mRNA levels of N-acetylglucosaminyltransferase III (GnT-III), a glycosyltransferase responsible for synthesizing a bisecting GlcNAc residue, were found highly expressed in the brains of AD patients. In our previous studies, glucagon-like peptide-1 (GLP-1) and its mimetics showed neuroprotective effects...
December 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29218078/extendin-4-protects-kidney-from-acute-ischemia-reperfusion-injury-through-upregulation-of-nrf2-signaling
#5
Yen-Yi Zhen, Chih-Chao Yang, Chi-Chih Hung, Chia-Chang Lee, Chen-Chang Lee, Chien-Hsing Wu, Yen-Ta Chen, Wei-Yu Chen, Kuan-Hung Chen, Hon-Kan Yip, Sheung-Fat Ko
This study tested the hypothesis that exendin-4 (Ex4) protects kidneys against ischemia-reperfusion (IR) injury mainly through upregulation of nuclear-factor erythroid 2-related factor 2 (Nrf2) signaling and downregulation of oxidative stress. Male-adult Sprague-Dawley rats (n=24) were equally divided into group 1 (sham-operated control), group 2 [IR only, ischemia (1 h)/reperfusion (72 h)] and group 3 (IR-Ex4, 10 μg/kg at 30 min, 24 h, 48 h after IR procedure). The in vitro study demonstrated that the protein expressions of phosphorylated (p)-Akt and Nrf2 were significantly progressively increased at time points of 0/0...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29216639/exendin-4-induces-bone-marrow-stromal-cells-migration-through-bone-marrow-derived-macrophages-polarization-via-pka-stat3-signaling-pathway
#6
Ning Wang, Jian Gao, Min Jia, Xue Ma, Zhanxiang Lei, Fei Da, Fei Yan, Huinan Zhang, Ying Zhou, Mingkai Li, Gonghao He, Jingru Meng, Xiaoxing Luo
BACKGROUND/AIMS: The synthesis and degradation processes involved in bone remodeling are critically regulated by osteoblasts and osteoclasts. The GLP-1 receptor agonist Exendin-4 is beneficial for osteoblast differentiation and increases the number of osteoblasts. METHODS: We constructed an ovariectomized model to evaluate the impact of Exendin-4 on bone formation in osteoporosis. A macrophage-depleted model was also created to investigate the effect of macrophages on bone formation...
December 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29206860/the-acute-glucose-lowering-effect-of-specific-gpr120-activation-in-mice-is-mainly-driven-by-glucagon-like-peptide-1
#7
Linda Sundström, Susanna Myhre, Monika Sundqvist, Andrea Ahnmark, William McCoull, Piotr Raubo, Sam D Groombridge, Magnus Polla, Ann-Christin Nyström, Lisbeth Kristensson, Mats Någård, Maria Sörhede Winzell
The mechanism behind the glucose lowering effect occurring after specific activation of GPR120 is not completely understood. In this study, a potent and selective GPR120 agonist was developed and its pharmacological properties were compared with the previously described GPR120 agonist Metabolex-36. Effects of both compounds on signaling pathways and GLP-1 secretion were investigated in vitro. The acute glucose lowering effect was studied in lean wild-type and GPR120 null mice following oral or intravenous glucose tolerance tests...
2017: PloS One
https://www.readbyqxmd.com/read/29177486/glucagon-like-peptide-1-inhibits-prandial-gastrointestinal-motility-through-myenteric-neuronal-mechanisms-in-humans
#8
Md Abdul Halim, Marie Degerblad, Magnus Sundbom, Urban Karlbom, Jens Juul Holst, Dominic-Luc Webb, Per M Hellström
Context: Glucagon-like peptide-1 (GLP-1) secretion from L-cells and postprandial inhibition of gastrointestinal motility. Objective: Investigate whether physiological plasma concentrations of GLP-1 can inhibit human postprandial gastrointestinal motility; determine target mechanism of GLP-1 and analogue ROSE-010 action. Design: Single-blind parallel study. Setting: University research laboratory. Participants: Healthy volunteers investigated with antroduodenojejunal manometry...
November 21, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29176623/microneedle-array-patches-loaded-with-dual-mineralized-protein-peptide-particles-for-type-2-diabetes-therapy
#9
Wei Chen, Rui Tian, Can Xu, Bryant C Yung, Guohao Wang, Yijing Liu, Qianqian Ni, Fuwu Zhang, Zijian Zhou, Jingjing Wang, Gang Niu, Ying Ma, Liwu Fu, Xiaoyuan Chen
The delivery of therapeutic peptides for diabetes therapy is compromised by short half-lives of drugs with the consequent need for multiple daily injections that reduce patient compliance and increase treatment cost. In this study, we demonstrate a smart exendin-4 (Ex4) delivery device based on microneedle (MN)-array patches integrated with dual mineralized particles separately containing Ex4 and glucose oxidase (GOx). The dual mineralized particle-based system can specifically release Ex4 while immobilizing GOx as a result of the differential response to the microenvironment induced by biological stimuli...
November 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29159483/obestatin-can-potentially-differentiate-wharton-s-jelly-mesenchymal-stem-cells-into-insulin-producing-cells
#10
Rana K El-Asfar, Mohamed M Kamal, Rania S Abd El-Razek, Ebtehal El-Demerdash, Hala O El-Mesallamy
In vitro-generation of β-cells from Wharton's jelly mesenchymal stem cells (WJ-MSCs) could provide a potential basis for diabetes mellitus cell therapy. However, the generation of functional insulin-producing cells (IPCs) from WJ-MSCs remains a challenge. Recently, obestatin, a gut hormone, was found to promote β-cell generation from pancreatic precursor cells. Accordingly, we hypothesize that obestatin can induce the differentiation of WJ-MSCs into IPCs. Therefore, the purpose of the current study is to examine the ability of obestatin to generate IPCs in comparison to well-known extrinsic factors that are commonly used in IPCs differentiation protocols from MSCs, namely exendin-4 and glucagon-like peptide-1 (GLP-1)...
November 20, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29157578/evaluation-of-the-insulinotropic-and-glucose-lowering-actions-of-zebrafish-gip-in-mammalian-systems-evidence-for-involvement-of-the-glp-1-receptor
#11
Galyna V Graham, J Michael Conlon, Yasser H Abdel-Wahab, Victor A Gault, Peter R Flatt
The insulinotropic properties of zebrafish GIP (zfGIP) were assessed in vitro using clonal pancreatic β-cell lines and isolated mouse islets and acute effects on glucose tolerance and insulin release in vivo were evaluated in mice. The peptide produced a dose-dependent increase in the rate of insulin release from BRIN-BD11 rat clonal β-cells at concentrations ≥30nM. Insulin release from 1.1 B4 human clonal β-cells and mouse islets was significantly increased by zfGIP (10nM and 1μM). The in vitro insulinotropic activity of zfGIP was decreased after incubating BRIN-BD11 cells with the GLP-1 receptor antagonist, exendin-4(9-39) (p<0...
November 17, 2017: Peptides
https://www.readbyqxmd.com/read/29136785/obestatin-prevents-h2o2-induced-damage-through-activation-of-trkb-in-rgc-5-cells
#12
Yang Liu, Yue-Xian Xing, Xin-Yuan Gao, Hong-Yu Kuang, Jing Zhang, Rong Liu
BACKGROUD: In the early stage of diabetic retinopathy, the damage of retinal ganglion cells already exists, promoting the development of the disease. The aim of this study was to investigate the protective role and the mechanisms of obestatin against H2O2-induced damage in RGC-5 cells. METHODS: RGC-5 cells were incubated with various concentrations of obestatin for 24h before H2O2 added. The survival rates of RGC-5 were measured by MTT assay. The expression of apoptosis-related proteins and TrkB pathway-related proteins were detected by Western blot analysis...
November 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29117623/comments-to-the-editor-concerning-the-paper-entitled-mitochondrial-dysfunction-in-diabetic-cardiomyopathy-e%C3%AF-ect-of-mesenchymal-stem-cell-with-ppar-%C3%AE-agonist-or-exendin-4-mohamed-abd-elaziz-wassef-et-al
#13
Alaaeldin Ahmed Hamza
No abstract text is available yet for this article.
November 8, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/29105359/glp-1-analogue-exendin-4-modulates-mapks-activity-but-not-the-heat-shock-response-in-human-hepg2-cells
#14
Dhanya Madhu, Maha Hammad, Sina Kavalakatt, Abdelkrim Khadir, Ali Tiss
PURPOSE: Glucagon-like peptide-1 (GLP-1) analogues reduce ER stress and inflammation in key metabolic organs, including the liver. However, their effects on heat shock response (HSR) and mitogen-activated protein kinases (MAPKs) have not yet been elucidated. In the present study, we investigated whether the GLP-1 analogue, exendin-4, triggers the expression of HSR and increases MAPK activity under metabolic stress. EXPERIMENTAL DESIGN: The effects of exendin-4 in the presence or absence of palmitic acid (PA; 400 μM) or glucose (30 mM) in the HepG2 liver cell line were assessed using Western blots, quantitative real-time PCR and label-free proteomics...
November 3, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29095895/exendin-4-a-glucagon-like-peptide-1-analogue-accelerates-healing-of-chronic-gastric-ulcer-in-diabetic-rats
#15
Yen-Cheng Chen, Ching-Chun Ho, Chih-Hsun Yi, Xiu-Zhu Liu, Tzu-Ting Cheng, Chen-Fuh Lam
BACKGROUND: Diabetes mellitus is an independent risk factor for impaired healing of peptic ulcers, and there are currently no supplementary therapeutics other than the standard antipeptic medicine to improve the ulcer healing in diabetes. This study examined the potential pleiotropic effect of a glucagon-like peptide (Glp)-1 analogue exendin (Ex)-4 on the regeneration of gastric ulcer in streptozotocin-induced diabetic rats. METHODS AND RESULTS: Chronic ulcer was created in rat stomach by submucosal injection of acetic acid and peri-ulcer tissues were analyzed 7 days after operation...
2017: PloS One
https://www.readbyqxmd.com/read/29094257/the-effects-of-exendin-4-on-bone-marrow-derived-mesenchymal-cells
#16
Paola Luciani, Benedetta Fibbi, Benedetta Mazzanti, Cristiana Deledda, Lara Ballerini, Alessandra Aldinucci, Susanna Benvenuti, Riccardo Saccardi, Alessandro Peri
PURPOSE: GLP-1 receptor agonists are antidiabetic drugs currently used in the therapy of type 2 diabetes. Despite several in vitro and in vivo animal studies suggesting a beneficial effect of GLP-1 analogues on bone, in humans their skeletal effects are not clear and clinical studies report conflicting results. METHODS: We differentiated human mesenchymal stromal cells (hMSC) toward the adipogenic and the osteoblastic lineages, analysing the effect of Exendin-4 (EXE) before, during and after specific differentiations...
November 1, 2017: Endocrine
https://www.readbyqxmd.com/read/29077992/population-pharmacokinetics-of-exendin-9-39-and-clinical-dose-selection-in-patients-with-congenital-hyperinsulinism
#17
Chee M Ng, Fei Tang, Steven Seeholzer, Yixuan Zou, Diva D De León
AIMS: Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycaemia in infants and children. Exendin-(9-39), an inverse glucagon-like peptide 1 (GLP-1) agonist, is a novel therapeutic agent for HI that has demonstrated glucose-raising effect. We reported the first population pharmacokinetic (PopPK) model of the exendin-(9-39) in patients with HI and proposed the optimal dosing regimen for future clinical trials in neonates with HI. METHODS: 182 pharmacokinetic (PK) observations from 26 subjects in three clinical studies were included for constructing the PopPK model using FOCE with interaction method in NONMEM...
October 27, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29074588/glp-1-elicits-an-intrinsic-gut-liver-metabolic-signal-to-ameliorate-diet-induced-vldl-overproduction-and-insulin-resistance
#18
Rituraj Khound, Jennifer Taher, Chris Baker, Khosrow Adeli, Qiaozhu Su
OBJECTIVE: Perturbations in hepatic lipid and very-low-density lipoprotein (VLDL) metabolism are involved in the pathogenesis of obesity and hepatic insulin resistance. The objective of this study is to delineate the mechanism of subdiaphragmatic vagotomy in preventing obesity, hyperlipidemia, and insulin resistance. APPROACH AND RESULTS: By subjecting the complete subdiaphragmatic vagotomized mice to various nutritional conditions and investigating hepatic de novo lipogenesis pathway, we found that complete disruption of subdiaphragmatic vagal signaling resulted in a significant decrease of circulating VLDL-triglyceride compared with the mice obtained sham procedure...
October 26, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29066599/il-6-type-cytokine-signaling-in-adipocytes-induces-intestinal-glp-1-secretion
#19
Stephan Wueest, Céline I Laesser, Marianne Böni-Schnetzler, Flurin Item, Fabrizio C Lucchini, Marcela Borsigova, Werner Müller, Marc Y Donath, Daniel Konrad
We recently showed that IL-6-type cytokine signaling in adipocytes induces FFA release from visceral adipocytes thereby promoting obesity-induced hepatic insulin resistance and steatosis. In addition, IL-6-type cytokines may increase the release of leptin from adipocytes and by that means induce GLP-1 secretion. We thus hypothesized that IL-6-type cytokine signaling in adipocytes may regulate insulin secretion. To this end, mice with adipocyte-specific knockout of gp130, the signal transducer protein of IL-6, were fed a high fat diet for 12 weeks...
October 24, 2017: Diabetes
https://www.readbyqxmd.com/read/29065926/glucagon-like-peptide-receptor-agonists-attenuate-advanced-glycation-end-products-induced-inflammation-in-rat-mesangial-cells
#20
Jui-Ting Chang, Yao-Jen Liang, Chia-Yu Hsu, Chao-Yi Chen, Po-Jung Chen, Yi-Feng Yang, Yen-Lin Chen, Dee Pei, Jin-Biou Chang, Jyh-Gang Leu
BACKGROUND: Hyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) production play major roles in progression of diabetic nephropathy. Anti-RAGE effect of peroxisome proliferator-activated receptor-delta (PPARδ) agonists was shown in previous studies. PPARδ agonists also stimulate glucagon-like peptide-1 (GLP-1) secretion from human intestinal cells. METHODS: In this study, the individual and synergic anti-inflammatory effects of GLP-1 receptor (exendin-4) and PPARδ (L-165,041) agonists in AGE-treated rat mesangial cells (RMC) were investigated...
October 24, 2017: BMC Pharmacology & Toxicology
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