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https://www.readbyqxmd.com/read/28542139/regulator-of-g-protein-signaling-2-is-a-key-regulator-of-pancreatic-%C3%AE-cell-mass-and-function
#1
H Dong, Y Zhang, J Wang, D S Kim, H Wu, B Sjögren, W Gao, L Luttrell, H Wang
Pancreatic β-cell death and dysfunction contributes to the pathogenesis of both type 1 and type 2 diabetes. We aimed to examine whether the regulator of G protein signaling protein 2 (RGS2), a multifunctional inhibitor of G protein-coupled receptor (GPCR) signaling, impacts β-cell death and function. Metabolic phenotypes, β-cell secretory function, and glucose and insulin tolerance were measured in RGS2 knockout (RGS2(-/-)) mice and their wild-type (RGS2(+/+)) littermate controls. β-Cell death was evaluated in RGS2-knockdown and -overexpressing β cells and RGS2(-/-) islets by flow cytometry, western blot, ELISA, TUNEL staining, and apoptosis RT(2) profiler PCR array analysis...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28532226/novel-biological-therapies-for-the-treatment-of-diabetic-foot-ulcers
#2
Jennifer Adeghate, Syed Nurulain, Kornélia Tekes, Erzsébet Fehér, Huba Kalász, Ernest Adeghate
The number of people with diabetes mellitus (DM) is estimated to exceed 640 million by the year 2040. Diabetic foot ulcer (DFU) is a debilitating illness that affects more than 2% of DM patients. DFU is caused by DM-induced neural and vascular lesions leading to a reduced sensation and microcirculation. The increase in the prevalence of DFU has prompted researchers to find new therapies for the management of DFU. Areas covered: This review presents the current status of novel biological therapies used in the treatment of DFU...
May 22, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28526921/glp-1-signalling-compensates-for-impaired-insulin-signalling-in-regulating-beta-cell-proliferation-in-%C3%AE-irko-mice
#3
Dan Kawamori, Jun Shirakawa, Chong Wee Liew, Jiang Hu, Tomoaki Morioka, Alokesh Duttaroy, Bryan Burkey, Rohit N Kulkarni
AIMS/HYPOTHESIS: We aimed to investigate potential interactions between insulin and glucagon-like peptide (GLP)-1 signalling pathways in the regulation of beta cell-cycle dynamics in vivo, in the context of the therapeutic potential of GLP-1 to modulate impaired beta cell function. METHODS: Beta cell-specific insulin receptor knockout (βIRKO) mice, which exhibit beta cell dysfunction and an age-dependent decrease in beta cell mass, were treated with the dipeptidyl peptidase-4 inhibitor vildagliptin...
May 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28513427/population-pharmacokinetics-of-lyophilized-recombinant-glucagon-like-peptide-1-receptor-agonist-recombinant-exendin-4-re-4-in-chinese-patients-with-type-2-diabetes-mellitus%C3%A2
#4
Yan-Nan Zang, Min-Jie Zhang, Yi-Tong Wang, Chen Wang, Qian Wang, Qing-Shan Zheng, Li-Nong Ji, Wei Guo, Yi Fang
OBJECTIVE: To investigate the population pharmacokinetics of lyophilized recombinant glucagon-like peptide-1 receptor agonist (rE-4) in Chinese patients with type 2 diabetes mellitus (T2DM) for plasma concentration estimation and individualized treatment. METHODS: Twelve patients with T2DM were enrolled to receive subcutaneous injections of rE-4 at 5 µg twice daily for 84 days. Administration dosage was adjusted from 5 µg to 10 µg twice daily at day 29 in case of glycated albumin (GA) ≥ 17%...
May 17, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28496193/exendin-4-exhibits-enhanced-anti-tumor-effects-in-diabetic-mice
#5
Lan He, Priscilla T Y Law, Chun Kwok Wong, Juliana C N Chan, Paul K S Chan
Type 2 diabetes (T2D) is associated with increased risk of cancers. In this connection, we previously demonstrated the promoting effect of diabetes on HPV-associated carcinogenesis using a xenograft model in db/db diabetic mice. The underlying mechanism of this observation might be partly contributed by dysregulated immune response in diabetes. In this study, we hypothesized that the impaired anti-tumor immune response in diabetic status could be modulated by exendin-4, a glucagon-like protein receptor agonist which exhibits anti-diabetic effects...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28464602/attenuation-of-high-glucose-induced-rat-cardiomyocyte-apoptosis-by-exendin-4-via-intervention-of-ho-1-nrf-2-and-the-pi3k-akt-signaling-pathway
#6
Shu-Mei Zhao, Hong-Li Gao, Yong-Liang Wang, Qing Xu, Chun-Yan Guo
Exendin-4, a glucagon-like peptide-1 receptor agonist, demonstrated cytoprotective actions beyond glycemic control in recent studies. The aims of the present study were to investigate the effects of exendin-4 on high glucose (HG)-induced cardiomyocyte apoptosis and the possible mechanisms. Rat cardiomyocytes were divided into 3 groups: normal glucose group (NG group), HG group and HG +exendin-4 group (HG+Ex Group). Cardiomyocyte apoptosis was evaluated by double-staining with annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) and flow cytometry...
April 30, 2017: Chinese Journal of Physiology
https://www.readbyqxmd.com/read/28461341/pglp-1-a-novel-long-acting-dual-function-glp-1-analog-ameliorates-streptozotocin-induced-hyperglycemia-and-inhibits-body-weight-loss
#7
Huashan Gao, Qian Zhao, Ziwei Song, Zhaocong Yang, You Wu, Shanshan Tang, Murad Alahdal, Yanfeng Zhang, Liang Jin
It is well known that glucagon-like peptide 1 (GLP-1) has antidiabetic action. It has 2 distinct functions, an insulinotropic effect dependent on GLP-1 receptor (GLP-1R) and an insulinomimetic effect independent of GLP-1R. However, use of GLP-1 in vivo is limited by its short half-life. Therefore, our lab designed PGLP-1, a novel 2-function candidate peptide as a potential substitute. Using a streptozotocin-induced hyperglycemic mouse model, we demonstrated in vitro and in vivo that PGLP-1 had insulinotropic actions dependent on GLP-1R and insulinomimetic functions independent of GLP-1R...
May 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28456941/activation-of-glucagon-like-peptide-1-receptor-promotes-neuroprotection-in-experimental-autoimmune-encephalomyelitis-by-reducing-neuroinflammatory-responses
#8
Chi-Ho Lee, Se Jin Jeon, Kyu Suk Cho, Eunjung Moon, Arjun Sapkota, Hee Sook Jun, Jong Hoon Ryu, Ji Woong Choi
The signaling axis of glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) has been an important component in overcoming diabetes, and recent reports have uncovered novel beneficial roles of this signaling axis in central nervous system (CNS) disorders, such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia, accelerating processes for exendin-4 repositioning. Here, we studied whether multiple sclerosis (MS) could be a complement to the CNS disorders that are associated with the GLP-1/GLP-1R signaling axis...
April 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28456436/centrally-located-glp-1-receptors-modulate-gastric-slow-waves-and-cardiovascular-function-in-ferrets-consistent-with-the-induction-of-nausea
#9
Zengbing Lu, Chi-Kong Yeung, Ge Lin, David T W Yew, P L R Andrews, John A Rudd
Glucagon-like peptide-1 (GLP-1) receptor agonists are indicated for the treatment of Type 2 diabetes and obesity, but can cause nausea and emesis in some patients. GLP-1 receptors are distributed widely in the brain, where they contribute to mechanisms of emesis, reduced appetite and aversion, but it is not known if these centrally located receptors also contribute to a modulation of gastric slow wave activity, which is linked causally to nausea. Our aim was to investigate the potential of the GLP-1 receptor agonist, exendin-4, administered into the 3rd ventricle to modulate emesis, feeding and gastric slow wave activity...
April 21, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28449155/mitochondrial-dysfunction-in-diabetic-cardiomyopathy-effect-of-mesenchymal-stem-cell-with-ppar-%C3%AE-agonist-or-exendin-4
#10
Mohamed Abd Elaziz Wassef, Ola M Tork, Laila A Rashed, Walaa Ibrahim, Heba Morsi, Dina Mohamed Mekawy Rabie
Therapy targeting mitochondria may provide novel ways to treat diabetes and its complications. Bone marrow-derived mesenchymal stem cells (MSCs), the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists and exendin-4; an analog of glucagon-like peptide-1 have shown cardioprotective properties in many cardiac injury models. So, we evaluated their effects in diabetic cardiomyopathy (DCM) in relation to mitochondrial dysfunction. This work included seven groups of adult male albino rats: the control group, the non-treated diabetic group, and the treated diabetic groups: one group was treated with MSCs only, the second with pioglitazone only, the third with MSCs and pioglitazone, the forth with exendin-4 only and the fifth with MSCs and exendin-4...
April 27, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28448133/design-of-novel-exendin-based-dual-glucagon-like-peptide-1-glp-1-glucagon-receptor-agonists
#11
Andreas Evers, Torsten Haack, Martin Lorenz, Martin Bossart, Ralf Elvert, Bernd Henkel, Siegfried Stengelin, Michael Kurz, Maike Glien, Angela Dudda, Katrin Lorenz, Dieter Kadereit, Michael Wagner
Dual activation of the glucagon-like peptide 1 (GLP-1) and glucagon receptor has the potential to lead to a novel therapy principle for the treatment of diabesity. Here, we report a series of novel peptides with dual activity on these receptors that were discovered by rational design. On the basis of sequence analysis and structure-based design, structural elements of glucagon were engineered into the selective GLP-1 receptor agonist exendin-4, resulting in hybrid peptides with potent dual GLP-1/glucagon receptor activity...
May 5, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28445811/liraglutide-a-glp-1-receptor-agonist-inhibits-vascular-smooth-muscle-cell-proliferation-by-enhancing-amp-activated-protein-kinase-and-cell-cycle-regulation-and-delays-atherosclerosis-in-apoe-deficient-mice
#12
Teruo Jojima, Kohsuke Uchida, Kazumi Akimoto, Takanori Tomotsune, Kazunori Yanagi, Toshie Iijima, Kunihiro Suzuki, Kikuo Kasai, Yoshimasa Aso
BACKGROUND AND AIMS: Several studies have demonstrated that both native glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists suppress the progression of atherosclerosis in animal models. METHODS: We investigated whether liraglutide, a GLP-1 analogue, could prevent the development of atherosclerosis in apolipoprotein E knockout mice (ApoE(-/-)) on a high-fat diet. We also examined the influence of liraglutide on angiotensin II-induced proliferation of rat vascular smooth muscle cells (VSMCs) via enhancement of AMP-activated protein kinase (AMPK) signaling and regulation of cell cycle progression...
April 7, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28439947/sirt1-hsf1-hsps-pathway-is-essential-for-exenatide-alleviated-lipid-induced-hepatic-endoplasmic-reticulum-stress
#13
Xiaobin Zheng, Fen Xu, Hua Liang, Huanyi Cao, Mengyin Cai, Wen Xu, Jianping Weng
Recent studies have indicated lipid-induced endoplasmic reticulum (ER) stress to be a major contributor to the progression of hepatic steatosis. Exenatide (Exendin-4), a glucagon-like peptide-1 receptor agonist, is known to improve hepatic steatosis with accumulating evidence. In this study, we investigated whether exenatide could alleviate lipid-induced hepatic ER stress through mammal sirtuin1 (SIRT1) and illustrated the detailed mechanisms. Male C57BL/6J mice challenged with a high-fat diet (HFD) were then treated with exenatide or normal saline by intraperitoneal injection for 4 weeks...
April 25, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28437610/long-acting-release-formulation-of-exendin-4-based-on-biomimetic-mineralization-for-type-2-diabetes-therapy
#14
Wei Chen, Guohao Wang, Bryant C Yung, Gang Liu, Zhiyong Qian, Xiaoyuan Chen
Exendin-4 has been clinically exploited for treating type 2 diabetes, but the short circulation half-life and multiple daily injections limit its widespread application with respect to poor patient compliance, low efficacy, and high treatment cost. In this study, a potent long-acting release system based on biomimetic mineralization was constructed for biocompatible and sustained exendin-4 delivery. Similar to natural biomineralization, exendin-4 can be mineralized to form nanosized mineral solids by means of the reaction between acidic amino acid residues and calcium ions in a supersaturated environment with negligible influence on peptide bioactivity...
April 27, 2017: ACS Nano
https://www.readbyqxmd.com/read/28430981/central-nervous-system-glp-1-receptors-regulate-islet-hormone-secretion-and-glucose-homeostasis-in-male-rats
#15
Lene Jessen, Eric P Smith, Yvonne Ulrich-Lai, James P Herman, Randy J Seeley, Darleen Sandoval, David D'Alessio
The glucagon-like peptide 1 (GLP-1) system plays an important role in blood glucose regulation, in great part through coordinate control of insulin and glucagon secretion. These effects are generally attributed to GLP-1 produced in peripheral sites, principally the intestine. GLP-1 is also produced in hindbrain neurons that signal through GLP-1 receptors (GLP-1r) expressed in brain regions involved in metabolic regulation. GLP-1 in the central nervous system (CNS) induces satiety, visceral illness, and stress responses...
April 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28405672/glucagon-like-peptide-1-related-peptides-increase-nitric-oxide-effects-to-reduce-platelet-activation
#16
Cristina Barale, Simona Buracco, Franco Cavalot, Chiara Frascaroli, Angelo Guerrasio, Isabella Russo
Glucagon-like peptide 1 (GLP-1) is object of intensive investigation for not only its metabolic effects but also the protective vascular actions. Since platelets exert a primary role in the pathogenesis of atherosclerosis, inflammation and vascular complications, we investigated whether GLP-1 directly influences platelet reactivity. For this purpose, in platelets from 72 healthy volunteers we evaluated GLP-1 receptor (GLP-1R) expression and the effects of a 15-minute incubation with the native form GLP-1(7-36), the N-terminally truncated form GLP-1(9-36) and the GLP-1 analogue Liraglutide (100 nmol/l) on: i) aggregation induced by collagen or arachidonic acid (AA); ii) platelet function under shear stress; iii) cGMP and cAMP synthesis and cGMP-dependent protein kinase (PKG)-induced Vasodilator-Stimulated-Phosphoprotein (VASP) phosphorylation; iv) activation of the signalling molecules Phosphatidylinositol 3-Kinase (PI3-K)/Akt and Mitogen Activated Protein Kinase (MAPK)/ERK-1/2; and v) oxidative stress...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28405188/compound-19e-a-novel-glucokinase-activator-protects-against-cytokine-induced-beta-cell-apoptosis-in-ins-1-cells
#17
Yoon Sin Oh, Eunhui Seo, Kaapjoo Park, Hee-Sook Jun
Previously, compound 19e, a novel heteroaryl-containing benzamide derivative, was identified as a potent glucokinase activator (GKA) and showed a glucose-lowering effect in diabetic mice. In this study, the anti-apoptotic actions of 19e were evaluated in INS-1 pancreatic beta-cells co-treated with TNF-α and IL-1β to induce cell death. Compound 19e protected INS-1 cells from cytokine-induced cell death, and the effect was similar to treatment with another GKA or exendin-4. Compound 19e reduced annexin-V stained cells and the expression of cleaved caspase-3 and poly (ADP-ribose) polymerase protein, as well as upregulated the expression of B-cell lymphoma-2 protein...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28400403/molecular-imaging-in-the-investigation-of-hypoglycaemic-syndromes-and-their-management
#18
David A Pattison, Rodney J Hicks
There has been recent progress in molecular imaging using a variety of cellular targets for the investigation of adult non-diabetic hypoglycaemic syndromes and its integration into patient management. These targets include peptide receptors - somatostatin receptors (SSTR) and glucagon-like peptide-1 receptor (GLP-1R) - the Amine Precursor Uptake and Decarboxylation system utilising the diphydroxyphenylaline (DOPA) analogue 6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine (18F-FDOPA), and glycolytic metabolism with 2-[18F]Fluoro-2-Deoxy-D-Glucose (FDG)...
April 11, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28396589/sphingosine-kinase-1-interacting-protein-is-a-novel-regulator-of-glucose-stimulated-insulin-secretion
#19
Yu Wang, Shin-Ichi Harashima, Yanyan Liu, Ryota Usui, Nobuya Inagaki
Glucose-stimulated insulin secretion (GSIS) is essential in keeping blood glucose levels within normal range. GSIS is impaired in type 2 diabetes, and its recovery is crucial in treatment of the disease. We find here that sphingosine kinase 1-interacting protein (SKIP, also called Sphkap) is highly expressed in pancreatic β-cells but not in α-cells. Intraperitoneal glucose tolerance test showed that plasma glucose levels were decreased and insulin levels were increased in SKIP(-/-) mice compared to SKIP(+/+) mice, but exendin-4-enhanced insulin secretion was masked...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28387682/exendin-4-treatment-improves-lps-induced-depressive-like-behavior-without-affecting-pro-inflammatory-cytokines
#20
Filip Ventorp, Cecilie Bay-Richter, Analise Sauro Nagendra, Shorena Janelidze, Viktor Sjödahl Matsson, Jack Lipton, Ulrika Nordström, Åsa Westrin, Patrik Brundin, Lena Brundin
BACKGROUND: Exendin-4 is a peptide agonist of the glucagon-like peptide-1 (GLP-1) receptor, currently in clinical trials as a potential disease-modifying therapy for Parkinson's disease. In light of this, it is important to understand potential modes of action of exendin-4 in the brain. Exendin-4 is neuroprotective and has been proposed to be directly anti-inflammatory, and that this is one way it reduces neurodegeneration. However, prior studies have focused on animal models involving both neurodegeneration and inflammation, therefore, it is also possible that the observed decreased inflammation is secondary to reduced neurodegeneration...
April 4, 2017: Journal of Parkinson's Disease
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