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Exendin-4

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https://www.readbyqxmd.com/read/29218078/extendin-4-protects-kidney-from-acute-ischemia-reperfusion-injury-through-upregulation-of-nrf2-signaling
#1
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
#2
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/29176623/microneedle-array-patches-loaded-with-dual-mineralized-protein-peptide-particles-for-type-2-diabetes-therapy
#3
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
#4
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
#5
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/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
#6
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
#7
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
#8
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
#9
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/29074588/glp-1-elicits-an-intrinsic-gut-liver-metabolic-signal-to-ameliorate-diet-induced-vldl-overproduction-and-insulin-resistance
#10
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/29065926/glucagon-like-peptide-receptor-agonists-attenuate-advanced-glycation-end-products-induced-inflammation-in-rat-mesangial-cells
#11
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
https://www.readbyqxmd.com/read/29064047/pancreatic-imaging-using-an-antibody-fragment-targeting-the-zinc-transporter-type-8-a-direct-comparison-with-radio-iodinated-exendin-4
#12
Olof Eriksson, Olle Korsgren, Ram Kumar Selvaraju, Marjorie Mollaret, Yann de Boysson, Fabrice Chimienti, Mohamed Altai
AIM: The zinc transporter 8 (ZnT8) has been suggested as a suitable target for non-invasive visualization of the functional pancreatic beta cell mass, due to both its pancreatic beta cell restricted expression and tight involvement in insulin secretion. METHODS: In order to examine the potential of ZnT8 as a surrogate target for beta cell mass, we performed mRNA transcription analysis in pancreatic compartments. A novel ZnT8 targeting antibody fragment Ab31 was radiolabeled with iodine-125, and evaluated by in vitro autoradiography in insulinoma and pancreas as well as by in vivo biodistribution...
October 24, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/29045658/exendin-4-a-glucagon-like-peptide-1-receptor-agonist-attenuates-breast-cancer-growth-by-inhibiting-nf-%C3%AE%C2%BAb-activation
#13
Chikayo Iwaya, Takashi Nomiyama, Shiho Komatsu, Takako Kawanami, Yoko Tsutsumi, Yuriko Hamaguchi, Tsuyoshi Horikawa, Yasuteru Yoshinaga, Shinichi Yamashita, Tomoko Tanaka, Yuichi Terawaki, Makito Tanabe, Kazuki Nabeshima, Akinori Iwasaki, Toshihiko Yanase
Incretin therapies have received significant attention because of their tissue-protective effects, which extend beyond those associated with glycemic control. Cancer is a primary cause of death in patients with diabetes mellitus. We previously reported anti-prostate cancer effects of the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonist exendin-4 (Ex-4). Breast cancer is one of the most common cancers in female patients with type 2 diabetes mellitus and obesity. Thus, we examined whether GLP-1 action could attenuate breast cancer...
October 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/29042458/exenatide-modulates-tumor-endothelial-cell-interactions-in-human-ovarian-cancer-cells
#14
Agnieszka Kosowska, Enrique Gallego-Colon, Wojciech Garczorz, Agnieszka Kłych-Ratuszny, Mohammad Reza F Aghdam, Michał Woz Niak, Andrzej Witek, Agnieszka Wróblewska-Czech, Anna Cygal, Jerzy Wojnar, Tomasz Francuz
Diabetes and cancer are prevalent diseases whose incidence is increasing globally. Diabetic women have a moderate risk increase in ovarian cancer, suggested to be due to an interaction between these two disorders. Furthermore, patients manifesting both diseases have associated worse prognosis, reduced survival and shorter relapse-free survival. According to current recommendations, incretin drugs such as Exenatide, a synthetic analog of Exendin-4, and Liraglutide are used as therapy for the type 2 diabetes (T2D)...
November 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29040320/circulating-microrna-375-as-biomarker-of-pancreatic-beta-cell-death-and-protection-of-beta-cell-mass-by-cytoprotective-compounds
#15
Imane Song, Sarah Roels, Geert A Martens, Luc Bouwens
OBJECTIVE: Previous studies demonstrated that circulating microRNA-375 (miR-375) is a suitable plasma biomarker for real-time detection of beta cell death. The present study evaluated the use of this biomarker to assess the beta cytoprotective effect of phenylpropenoic acid glucoside (PPAG), which was previously demonstrated to protect beta cells against various types of injury, and of exendin-4, which is an established antidiabetic drug. METHODS: PPAG or exendin-4 were administered in mice treated with streptozotocin (STZ) to acutely induce beta cell death...
2017: PloS One
https://www.readbyqxmd.com/read/29022064/proinflammatory-switch-from-g%C3%AE-s-to-g%C3%AE-i-signaling-by-glucagon-like-peptide-1-receptor-in-murine-splenic-monocyte-following-burn-injury
#16
Qing-Hong Zhang, Ji-Wei Hao, Guang-Lei Li, Xiao-Jing Ji, Xu-Dong Yao, Ning Dong, Yong-Ming Yao
OBJECTIVE: Glucagon-like peptide-1 (GLP-1)-based therapy via G protein-coupled receptor (GPCR) GLP-1R, to attenuate hyperglycemia in critical care has attracted great attention. However, the exaggerated inflammation by GLP-1R agonist, Exendin-4, in a mouse model of burn injury was quite unexpected. Recent studies found that GPCR might elicit proinflammatory effects by switching from Gαs to Gαi signaling in the immune system. Thus, we aimed to investigate the possible Gαs to Gαi switch in GLP-1R signaling in monocyte following burn injury...
October 11, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28986282/exendin-4-attenuates-neuronal-death-via-glp-1r-pi3k-akt-pathway-in-early-brain-injury-after-subarachnoid-hemorrhage-in-rats
#17
Zhiyi Xie, Budbazar Enkhjargal, Lingyun Wu, Keren Zhou, Chengmei Sun, Xin Hu, Vadim Gospodarev, Jiping Tang, Chao You, John H Zhang
Neuronal apoptosis is considered to be a crucial therapeutic target against early brain injury (EBI) after subarachnoid hemorrhage (SAH). Emerging evidence indicates that Exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, plays a neuroprotective role in cerebrovascular disease. This study was conducted in order to verify the neuroprotective role of EX-4 in EBI after SAH in rats. The endovascular perforation model of SAH was performed in Sprague-Dawley rats (n = 153). Ex-4 was intraperitoneally injected 1 h after SAH induction in the rats (SAH + Ex-4)...
October 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28953210/99mtc-exendin-9-39-octreotide-biokinetics-and-radiation-dosimetry-in-healthy-individuals
#18
Blanca E Ocampo-García, Clara L Santos-Cuevas, Myrna A Luna-Gutiérrez, Eleazar Ignacio-Alvarez, Martha Pedraza-López, Cesar Manzano-Mayoral
AIM: About 90% of insulinomas are benign and 5-15% are malignant. Benign insulinomas express the glucagon-like peptide-1 receptor (GLP-1R, which recognizes exendin-4 and low levels of the somatostatin receptor (SSTR, which recognizes octreotide), whereas malignant insulinomas overexpress SSTR and low levels of GLP-1R. Recently, Lys(Tc-EDDA/HYNIC)-exendin(9-39)/Tc-EDDA/HYNIC-Tyr-octreotide was formulated to detect 100% of insulinomas. The aim of this study was to estimate the biokinetics and dosimetry of Tc-exendin(9-39)/octreotide in four healthy individuals...
November 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/28947919/glucagon-like-peptide-1-receptor-agonist-exendin-4-protects-against-interleukin-1%C3%AE-mediated-inhibition-of-glucose-stimulated-insulin-secretion-by-mouse-insulinoma-%C3%AE-cells
#19
Ben Niu, Chao Li, Heng Su, Qingzhu Li, Qiu He, Lijuan Liu, Yuanming Xue, Tao Shen, Xueshan Xia
The aim of the present study was to investigate the protective effect of the glucagon-like peptide-1 receptor agonist exendin-4 on the interleukin (IL)-1β-induced impairment of glucose-stimulated insulin secretion (GSIS) in β-TC-6 cells. β-TC-6 cells were pretreated with various concentrations of IL-1β (0.15, 1.5 or 15 ng/ml) and exendin-4 (0.1 or 1 mM). Exendin-4 was administered to β-TC-6 cells prior to, during and following pretreatment. Cells were stimulated with various concentrations of glucose (0, 1...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28947828/fenugreek-compound-n55-lowers-plasma-glucose-through-the-enhancement-of-response-of-physiological-glucagon-like-peptide-1
#20
I-Wen Chou, Yu-Hong Cheng, Yet-Ran Chen, Patrick Ching-Ho Hsieh, Klim King
Glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) analogues are approved for treating type 2 diabetes, but are known to activate GLP-1R signaling globally and constitutively. Active compound N55, previously isolated from fenugreek, enhances the potency of GLP-1 without activating GLP-1R. Here we investigated if N55 lowers plasma glucose base on physiological levels of GLP-1. N55 was found to dose-dependently lower plasma glucose in non-fasted mice but not in the fasted mice, with the effect attenuated by GLP-1R antagonist exendin-(9-39) (Ex-9)...
September 25, 2017: Scientific Reports
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