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https://www.readbyqxmd.com/read/28449155/mitochondrial-dysfunction-in-diabetic-cardiomyopathy-effect-of-mesenchymal-stem-cell-with-ppar-%C3%AE-agonist-or-exendin-4
#1
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
#2
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. Based on 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...
April 27, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28365524/pancreas-and-liver-uptake-of-new-radiolabeled-incretins-glp-1-and-exendin-4-in-models-of-diet-induced-and-diet-restricted-obesity
#12
Daniele Seo, Bluma Linkowski Faintuch, Erica Aparecida de Oliveira, Joel Faintuch
INTRODUCTION: Radiolabeled GLP-1 and its analog Exendin-4, have been employed in diabetes and insulinoma. No protocol in conventional Diet-Induced Obesity (DIO), and Diet-Restricted Obesity (DRO), has been identified. Aiming to assess pancreatic beta cell uptake in DIO and DRO, a protocol was designed. METHODS: GLP-1-βAla-HYNIC and HYNIC-βAla-Exendin-4 were labeled with technetium-99m. Four Swiss mouse models were adopted: Controls (C), Alloxan Diabetes Controls (ADC), DIO and DRO...
March 18, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28356733/a-novel-selective-vpac2-agonist-peptide-conjugated-chitosan-modified-selenium-nanoparticles-with-enhanced-anti-type-2-diabetes-synergy-effects
#13
Shao-Jun Zhao, De-Hua Wang, Yan-Wei Li, Lei Han, Xing Xiao, Min Ma, David Chi-Cheong Wan, An Hong, Yi Ma
A novel neuroendocrine peptide, pituitary adenylate cyclase activating peptide (PACAP), was found to have an important role in carbohydrate or lipid metabolism and was susceptible to dipeptidyl peptidase IV degradation. It can not only mediate glucose-dependent insulin secretion and lower blood glucose by activating VPAC2 receptor, but also raise blood glucose by promoting glucagon production by VPAC1 receptor activation. Therefore, its therapeutic application is restricted by the exceedingly short-acting half-life and the stimulatory function for glycogenolysis...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28355142/effects-of-adrenomedullin-and-glucagon-like-peptide-on-distal-flap-necrosis-and-vascularity-the-role-of-receptor-systems-and-nitric-oxide
#14
Betul Cam, Deniz Bagdas, M Ozgur Ozyigit, Engin Sagdilek, Naciye Isbil Buyukcoskun, Kasım Ozluk
OBJECTIVE: Flap necrosis in the distal area due to the deficiency of blood circulation is a major complication in flap treatment. In many previous studies, some natural substances such as chlorogenic acid, adrenomedullin (ADM), and glucagon-like peptide-1 (GLP-1) have been used to improve flap viability via their vasodilator, angiogenic, and antioxidant effects. The aim of this study is to clarify the mechanism through the use of selective antagonists for calcitonin gene-related peptide (CGRP) receptors and GLP-1 receptors such as CGRP-(8-37), exendin-(9-39), respectively, in the flap healing effects of ADM and GLP-1...
March 24, 2017: Wounds: a Compendium of Clinical Research and Practice
https://www.readbyqxmd.com/read/28347868/teneligliptin-a-dipeptidyl-peptidase-4-inhibitor-attenuated-pro-inflammatory-phenotype-of-perivascular-adipose-tissue-and-inhibited-atherogenesis-in-normoglycemic-apolipoprotein-e-deficient-mice
#15
Hotimah Masdan Salim, Daiju Fukuda, Yasutomi Higashikuni, Kimie Tanaka, Yoichiro Hirata, Shusuke Yagi, Takeshi Soeki, Michio Shimabukuro, Masataka Sata
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have various cellular effects that are associated with vascular protection. Here, we examined whether teneligliptin alters the pro-inflammatory phenotype of perivascular adipose tissue (PVAT) and inhibits atherogenesis. METHODS AND RESULTS: Teneligliptin (60mg/kg/day) was administered orally to apolipoprotein-E-deficient (ApoE(-/-)) mice for 20weeks. Teneligliptin significantly inhibited the development of atherosclerosis in the aortic arch compared with vehicle (P<0...
March 24, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28342399/design-synthesis-and-biological-evaluation-of-pegylated-xenopus-glucagon-like-peptide-1-derivatives-as-long-acting-hypoglycemic-agents
#16
Jing Han, Yiyun Wang, Qinghua Meng, Guangchao Li, Fangmin Huang, Su Wu, Yingying Fei, Feng Zhou, Junjie Fu
In order to develop novel long-acting GLP-1 derivatives, a peptide hybrid (1a) from human GLP-1 and Xenopus GLP-1 discovered in our previous research was selected as the lead compound. Exendin-4 inspired modification resulted in peptide 1b with enhanced glucose-lowering activity. Cysteine mutated 1b derivatives with reserved bioactivity were further site-specifically connected with mPEG2000-MAL to provide conjugates 3a-h, among which 3d and 3e were found to have significantly improved hypoglycemic activity and insulinotropic ability than GLP-1...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28337255/combined-therapy-with-melatonin-and-exendin-4-effectively-attenuated-the-deterioration-of-renal-function-in-rat-cardiorenal-syndrome
#17
Kuan-Hung Chen, Chih-Hung Chen, Christopher Glenn Wallace, Yen-Ta Chen, Chih-Chao Yang, Pei-Hsun Sung, Hsin-Ju Chiang, Yi-Ling Chen, Sarah Chua, Hon-Kan Yip, Jiin-Tsuey Cheng
This study tested the hypothesis that combined therapy with melatonin (Mel) and exendin-4 (Ex4) would be superior to either therapy alone for preventing the deterioration of renal function in cardiorenal syndrome (CRS). Male adult Sprague Dawley rats (n = 48) were randomly and equally divided into sham-control (SC), chronic kidney disease (CKD; induced by 5/6 nephrectomy), CRS (CKD + dilated cardiomyopathy, DCM; induced by doxorubicin 7 mg/kg i.p. every 5 days, 4 doses), CRS-Mel (20 mg/kg/day), CRS-Ex4 (10 µg/kg/day) and CRS-Mel-Ex4...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28334990/insulin-resistance-and-exendin-4-treatment-for-multiple-system-atrophy
#18
Fares Bassil, Marie-Hélène Canron, Anne Vital, Erwan Bezard, Yazhou Li, Nigel H Greig, Seema Gulyani, Dimitrios Kapogiannis, Pierre-Olivier Fernagut, Wassilios G Meissner
Multiple system atrophy is a fatal sporadic adult-onset neurodegenerative disorder with no symptomatic or disease-modifying treatment available. The cytopathological hallmark of multiple system atrophy is the accumulation of α-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Impaired insulin/insulin-like growth factor-1 signalling (IGF-1) and insulin resistance (i.e. decreased insulin/IGF-1) have been reported in other neurodegenerative disorders such as Alzheimer's disease. Increasing evidence also suggests impaired insulin/IGF-1 signalling in multiple system atrophy, as corroborated by increased insulin and IGF-1 plasma concentrations in multiple system atrophy patients and reduced IGF-1 brain levels in a transgenic mouse model of multiple system atrophy...
March 14, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28325479/the-role-of-pancreatic-preproglucagon-in-glucose-homeostasis-in-mice
#19
Adam P Chambers, Joyce E Sorrell, April Haller, Karen Roelofs, Chelsea R Hutch, Ki-Suk Kim, Ruth Gutierrez-Aguilar, Bailing Li, Daniel J Drucker, David A D'Alessio, Randy J Seeley, Darleen A Sandoval
Glucagon-like peptide 1 (GLP-1) is necessary for normal gluco-regulation, and it has been widely presumed that this function reflects the actions of GLP-1 released from enteroendocrine L cells. To test the relative importance of intestinal versus pancreatic sources of GLP-1 for physiological regulation of glucose, we administered a GLP-1R antagonist, exendin-[9-39] (Ex9), to mice with tissue-specific reactivation of the preproglucagon gene (Gcg). Ex9 impaired glucose tolerance in wild-type mice but had no impact on Gcg-null or GLP-1R KO mice, suggesting that Ex9 is a true and specific GLP-1R antagonist...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28318339/exendin-4-does-not-modify-growth-or-apoptosis-of-human-colon-cancer-cells
#20
He Wenjing, Yu Shuang, Li Weisong, Xiao Haipeng
AIM: Glucagon-like peptide-1 (GLP-1) receptor agonists are a kind of very popular antidiabetes drugs. They promote cell proliferation and survival through activation of signaling pathways in human islet cells involving phosphate idylinositol 3 kinase (PI3K) and extracellular regulated kinases 1 and 2 (ERK1/2), which are frequently activated in human colon cancer cells. Then, it is possible that taking GLP-1 receptor (GLP-1R) agonists persistently would induce proliferation of β cells as well as colon cancer cells...
March 20, 2017: Endocrine Research
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