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Exendin-4

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https://www.readbyqxmd.com/read/28337255/combined-therapy-with-melatonin-and-exendin-4-effectively-attenuated-the-deterioration-of-renal-function-in-rat-cardiorenal-syndrome
#1
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
#2
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/28318339/exendin-4-does-not-modify-growth-or-apoptosis-of-human-colon-cancer-cells
#3
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
https://www.readbyqxmd.com/read/28315693/central-glp-1-receptor-activation-modulates-cocaine-evoked-phasic-dopamine-signaling-in-the-nucleus-accumbens-core
#4
Samantha M Fortin, Mitchell F Roitman
Drugs of abuse increase the frequency and magnitude of brief (1-3s), high concentration (phasic) dopamine release events in terminal regions. These are thought to be a critical part of drug reinforcement and ultimately the development of addiction. Recently, metabolic regulatory peptides, including the satiety signal glucagon-like peptide-1 (GLP-1), have been shown to modulate cocaine reward-driven behavior and sustained dopamine levels after cocaine administration. Here, we use fast-scan cyclic voltammetry (FSCV) to explore GLP-1 receptor (GLP-1R) modulation of dynamic dopamine release in the nucleus accumbens (NAc) during cocaine administration...
March 15, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28283573/genetically-encoded-photocrosslinkers-determine-the-biological-binding-site-of-exendin-4-in-the-n-terminal-domain-of-the-intact-human-glucagon-like-peptide-1-receptor-glp-1r
#5
Cassandra Koole, Christopher A Reynolds, Juan C Mobarec, Caroline Hick, Patrick M Sexton, Thomas P Sakmar
The glucagon-like peptide-1 receptor (GLP-1R) is a key therapeutic target in the management of type II diabetes mellitus, with actions including regulation of insulin biosynthesis and secretion, promotion of satiety and preservation of β-cell mass. Like most class B G protein-coupled receptors (GPCRs), there is limited knowledge linking biological activity of the GLP-1R with the molecular structure of an intact, full-length, functional receptor-ligand complex. In this study, we have utilized genetic code expansion to site-specifically incorporate the photoactive amino acid p-azido-L-phenylalanine (azF) into N-terminal residues of a full-length, functional human GLP-1R in mammalian cells...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28282854/systematic-design-of-trypsin-cleavage-site-mutated-exendin4-cysteine-1-an-orally-bioavailable-glucagon-like-peptide-1-receptor-agonist
#6
Wenbo Sai, Hong Tian, Kangmin Yang, Daoqi Tang, Jinxiao Bao, Yang Ge, Xiaoda Song, Yu Zhang, Cheng Luo, Xiangdong Gao, Wenbing Yao
Exendin-4 is a strong therapeutic candidate for the treatment of metabolic syndrome. Related receptor agonist drugs have been on the market since 2005. However, technical limitations and the pain caused by subcutaneous injection have severely limited patient compliance. The goal of the study is to investigate a biologically active exendin-4 analog could be administered orally. Using intraperitoneal glucose tolerance tests, we discovered that exendin4-cysteine administered by oral gavage had a distinct hypoglycemic effect in C57BL/6J mice...
March 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28242257/exendin-4-inhibits-structural-remodeling-and-improves-ca-2-homeostasis-in-rats-with-heart-failure-via-the-glp-1-receptor-through-the-enos-cgmp-pkg-pathway
#7
Jingjing Chen, Dandan Wang, Fangai Wang, Shaobo Shi, Yuting Chen, Bo Yang, Yanhong Tang, Congxin Huang
The glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 is a long-acting analog of GLP-1, which stimulates insulin secretion and is clinically used in the treatment of type 2 diabetes. Previous studies have demonstrated that GLP-1 agonists and analogs serve as cardioprotective factors in various conditions. Disturbances in calcium cycling are characteristic of heart failure (HF); therefore, the aim of this study was to investigate the effect of exendin-4 (a GLP-1 mimetic) on the regulation of calcium handling and to identify the underlying mechanisms in an HF rat model after myocardial infarction (MI)...
February 24, 2017: Peptides
https://www.readbyqxmd.com/read/28223210/a-novel-glp-1-gip-dual-receptor-agonist-protects-from-6-ohda-lesion-in-a-rat-model-of-parkinson-s-disease
#8
Jaishree Jalewa, Mohit Kumar Sharma, Simon Gengler, Christian Hölscher
The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. GLP-1 analogues are currently on the market as treatments for type II diabetes. We previously showed that the novel dual agonist (DA-JC1) was effective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
February 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28202074/exendin-4-in-combination-with-adipose-derived-stem-cells-promotes-angiogenesis-and-improves-diabetic-wound-healing
#9
Eunhui Seo, Jae Soo Lim, Jin-Bum Jun, Woohyuk Choi, In-Sun Hong, Hee-Sook Jun
BACKGROUND: Diminished wound healing is a major complication of diabetes mellitus and can lead to foot ulcers. However, there are limited therapeutic methods to treat this condition. Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, is known to have many beneficial effects on diabetes. In addition, mesenchymal stem cells are known to have wound healing effects. We investigated the effects of Ex-4 in combination with human adipose tissue-derived stem cells (ADSCs) on diabetic wound healing in a diabetic animal model...
February 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28188238/vmp1-related-autophagy-induced-by-fructose-rich-diet-in%C3%A2-%C3%AE-cells-it-s-prevention-by-incretins
#10
Bárbara Maiztegui, Verónica Boggio, Carolina Lisi Román, Luis Emilio Flores, Héctor Del Zotto, Alejandro Ropolo, Daniel Grasso, María Inés Vaccaro, Juan José Gagliardino
Aim : To demonstrate the role of autophagy and incretins on fructose-induced alteration in β-cell mass and function. Methods : Normal Wistar rats were fed (3 weeks) with commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrine parameters, β-cell mass, morphology/ultrastructure and apoptosis, VMP1 expression and glucose-stimulated insulin secretion (GSIS) were studied. Complementary, islets isolated from normal rats were cultured (3 days) without (C) or with F and F plus exendin-4 (FE) or chloroquine (FCQ)...
February 10, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28134698/68ga-exendin-4-pet-ct-in-evaluation-of-endoscopic-ultrasound-guided-ethanol-ablation-of-an-insulinoma
#11
Yaping Luo, Ji Li, Aiming Yang, Hongbo Yang, Fang Li
A 32-year-old man with endogenous hyperinsulinemic hypoglycemia was clinically diagnosed with an insulinoma. Conventional imaging result was negative, and a previous exploratory laparotomy with distal pancreatectomy failed to detect the tumor. Ga-exendin-4 PET/CT showed a lesion with intense radioactivity in the head of the pancreas suggestive of an insulinoma, and endoscopic ultrasound-guided ethanol ablation was performed. Postablation evaluation with Ga-exendin-4 PET/CT showed markedly decreased radioactivity of the tumor...
January 27, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28122026/exendin-4-upregulates-adiponectin-level-in-adipocytes-via-sirt1-foxo-1-signaling-pathway
#12
Anping Wang, Ting Li, Ping An, Wenhua Yan, Hua Zheng, Baoan Wang, Yiming Mu
Glucagon-like peptide-1 (GLP-1) receptor plays an essential role in regulating glucose metabolism. GLP-1 receptor agonists have been widely used for treating diabetes and other insulin resistance-related diseases. However, mechanisms underlying the anti-diabetic effects of GLP-1 receptor agonists remain largely unknown. In this study, we investigated the effects of GLP-1 agonist exendin-4 on the expression of adiponectin, an insulin sensitizing hormone. We found that exendin-4 increased the expression and secretion of adiponectin both in vitro and in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28103285/radioiodinated-exendin-4-is-superior-to-the-radiometal-labelled-glucagon-like-peptide-1-receptor-probes-overcoming-their-high-kidney-uptake
#13
Tilman Läppchen, Roswitha Tönnesmann, Jos Eersels, Philipp T Meyer, Helmut R Maecke, Svetlana N Rylova
GLP-1 receptors are ideal targets for preoperative imaging of benign insulinoma and for quantifying the beta cell mass. The existing clinical tracers targeting GLP-1R are all agonists with low specific activity and very high kidney uptake. In order to solve those issues we evaluated GLP-1R agonist Ex-4 and antagonist Ex(9-39) radioiodinated at Tyr40 side by side with [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]Ex-4 (68Ga-Ex-4) used in the clinic. The Kd, Bmax, internalization and binding kinetics of [Nle14,125I-Tyr40-NH2]Ex-4 and [Nle14,125I-Tyr40-NH2]Ex(9-39) were studied in vitro using Ins-1E cells...
2017: PloS One
https://www.readbyqxmd.com/read/28103022/discovery-of-a-novel-series-of-orally-bioavailable-and-cns-penetrant-glucagon-like-peptide-1-receptor-glp-1r-noncompetitive-antagonists-based-on-a-1-3-disubstituted-7-aryl-5-5-bis-trifluoromethyl-5-8-dihydropyrimido-4-5-d-pyrimidine-2-4-1h-3h-dione-core
#14
Kellie D Nance, Emily L Days, C David Weaver, Anastasia Coldren, Tiffany D Farmer, Hyekyung P Cho, Colleen M Niswender, Anna L Blobaum, Kevin D Niswender, Craig W Lindsley
A duplexed, functional multiaddition high throughput screen and subsequent optimization effort identified the first orally bioavailable and CNS penetrant glucagon-like peptide-1 receptor (GLP-1R) noncompetitive antagonist. Antagonist 5d not only blocked exendin-4-stimulated insulin release in islets but also lowered insulin levels while increasing blood glucose in vivo.
February 3, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28095743/adult-murine-pancreatic-progenitors-require-epidermal-growth-factor-and-nicotinamide-for-self-renewal-and-differentiation-in-a-serum-and-conditioned-medium-free-culture
#15
Lena Wedeken, Angela Luo, Jacob R Tremblay, Jeffrey Rawson, Liang Jin, Dan Gao, Janine Quijano, Hsun Teresa Ku
Adult pancreatic stem and progenitor cells may serve as an alternative source of insulin-secreting endocrine cells in cell replacement therapy for type 1 diabetes, but much remained unknown about these cells. We previously identified adult murine pancreatic progenitor-like cells that displayed in vitro self-renewal and tri-lineage differentiation activities in a three-dimensional colony/organoid assay containing 1% methylcellulose and 5% Matrigel. However, the presence of other undefined culture components, such as serum and conditioned medium, has prevented a complete understanding of the signals required for progenitor cell growth...
January 17, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28088959/-effect-of-exendin-4-on-lipid-deposition-in-skeletal-muscle-of-diet-induced-obese-mice-and-its-underlying-mechanism
#16
H Y Cao, F Xu, Z L Chen, B S Lin, X B Zheng, S H Yuan, H Liang, J P Weng
Objective: To investigate the effect of exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, on reducing lipid deposition and improving insulin resistance in skeletal muscle and the underlying mechanisms in high-fat diet (HFD)-induced obese mice. Methods: Twelve male C57BL/6J mice were challenged with HFD for 12 weeks to induce obesity and then randomly divided into two groups: exendin-4 group (intraperitoneal injection of 24 nmol·kg(-1)·d(-1) exendin-4 for 4 weeks) and HFD group (intraperitoneal injection of normal saline for 4 weeks), with 6 mice in each group...
January 10, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28057699/glucagon-like-peptide-1-and-its-analogues-act-in-the-dorsal-raphe-and-modulate-central-serotonin-to-reduce-appetite-and-body-weight
#17
Rozita H Anderberg, Jennifer E Richard, Kim Eerola, Lorena Lopez Ferreras, Elin Banke Nordbeck, Caroline Hansson, Hans Nissbrandt, Filip Berqquist, Fiona M Gribble, Frank Reimann, Ingrid Wernstedt-Asterholm, Christophe Lamy, Karolina P Skibicka
Glucagon-like peptide-1 (GLP-1) and serotonin play critical roles in energy balance regulation. Both systems are exploited clinically as anti-obesity strategies. Surprisingly whether they interact in order to regulate energy balance is poorly understood. Here we investigated mechanisms by which GLP-1 and serotonin interact at the level of the CNS. Serotonin depletion impaired the ability of exendin-4, a clinically utilized GLP-1 analogue, to reduce body weight in rats, suggesting serotonin is a critical mediator of the energy balance impact of GLP-1R activation...
January 5, 2017: Diabetes
https://www.readbyqxmd.com/read/28043300/-influences-of-exendin-4-on-the-secretion-function-of-islet-beta-cells-from-rats-in-the-early-stage-of-severe-scald
#18
D X Zhao, L Ma, Z A Shen, D W Li, Y R Shang, K Yin, W F Cheng, X Wang, Z X Liu
Objective: To observe the secretion function changes of islet beta cells isolated from rats in the early stage of severe scald, and to explore the influence of them. Methods: Thirty-six Wistar rats were divided into sham injury (SI) group, sham injury+ exendin-4 (SIE) group, scald (S) group, and scald+ exendin-4 (SE) group according to the random number table, with 9 rats in each group. Rats in groups S and SE were inflicted with 50% total body surface area full-thickness scald by a 12-s immersion of back and a 6-s immersion of abdomen in 94 ℃ hot water...
December 20, 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/27997588/protective-effects-of-vildagliptin-against-pioglitazone-induced-bone-loss-in-type-2-diabetic-rats
#19
Young Sil Eom, A-Ryeong Gwon, Kyung Min Kwak, Ju-Young Kim, Seung Hee Yu, Sihoon Lee, Yeun Sun Kim, Ie Byung Park, Kwang-Won Kim, Kiyoung Lee, Byung-Joon Kim
Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model...
2016: PloS One
https://www.readbyqxmd.com/read/27993221/exendin-4-a-glucagon-like-peptide-1-analogue-accelerates-diabetic-wound-healing
#20
Jun-Neng Roan, Han-Ni Cheng, Chao-Chung Young, Chi-Ju Lee, Ming-Long Yeh, Chwan-Yau Luo, Yau-Sheng Tsai, Chen-Fuh Lam
BACKGROUND: Diabetes disregulates inflammatory responses and impairs vascular function in wounds. Glucagon-like peptide-1 receptor (Glp-1R) agonists are hypoglycemic agents with pleiotropic vascular protective and anti-inflammatory effects. The therapeutic potential of a Glp-1 analogue in a diabetic rat model of excisional wound injury was investigated. MATERIALS AND METHODS: Excisional wounds were created on the dorsum of streptozotocin-induced diabetic rats, which received placebo or Glp-1 analogue exendin-4 (Ex4; 0...
February 2017: Journal of Surgical Research
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