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Exendin-4

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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
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/27957723/low-kidney-uptake-of-glp-1r-targeting-beta-cell-specific-pet-tracer-18-f-labeled-nle-14-lys-40-exendin-4-analog-shows-promise-for-clinical-imaging
#6
Kirsi Mikkola, Cheng-Bin Yim, Paula Lehtiniemi, Saila Kauhanen, Miikka Tarkia, Tuula Tolvanen, Pirjo Nuutila, Olof Solin
BACKGROUND: Several radiometal-labeled, exendin-based tracers that target glucagon-like peptide-1 receptors (GLP-1R) have been intensively explored for β cell imaging. The main obstacle has been the high uptake of tracer in the kidneys. This study aimed to develop a novel GLP1-R-specific tracer, with fluorine-18 attached to exendin-4, to label β cells for clinical imaging with PET (positron emission tomography). We hypothesized that this tracer would undergo reduced kidney uptake. (18)F-labeled [Nle(14),Lys(40)]exendin-4 analog ([(18)F]exendin-4) was produced via Cu-catalyzed click chemistry...
December 2016: EJNMMI Research
https://www.readbyqxmd.com/read/27941938/effects-of-exendin-4-on-human-adipose-tissue-inflammation-and-ecm-remodelling
#7
E Pastel, S Joshi, B Knight, N Liversedge, R Ward, K Kos
BACKGROUND/OBJECTIVES: Subjects with type-2 diabetes are typically obese with dysfunctional adipose tissue (AT). Glucagon-like peptide-1 (GLP-1) analogues are routinely used to improve glycaemia. Although, they also aid weight loss that improves AT function, their direct effect on AT function is unclear. To explore GLP-1 analogues' influence on human AT's cytokine and extracellular matrix (ECM) regulation, we therefore obtained and treated omental (OMAT) and subcutaneous (SCAT) AT samples with Exendin-4, an agonist of the GLP-1 receptor (GLP-1R)...
December 12, 2016: Nutrition & Diabetes
https://www.readbyqxmd.com/read/27939242/ex4-stabilizes-and-activates-nrf2-via-pkc%C3%AE-contributing-to-the-prevention-of-oxidative-stress-induced-pancreatic-beta-cell-damage
#8
Mi-Hwi Kim, Eung-Hwi Kim, Hye Seung Jung, Dongki Yang, Eun-Young Park, Hee-Sook Jun
Oxidative stress in pancreatic beta cells can inhibit insulin secretion and promote apoptotic cell death. Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, can suppress beta cell apoptosis, improve beta cell function and protect against oxidative damage. In this study, we investigated the molecular mechanisms for antioxidative effects of EX4 in pancreatic beta cells. INS-1 cells, a rat insulinoma cell line, were pretreated with EX4 and exposed to palmitate or H2O2. Reactive oxygen species (ROS) production, and glutathione and insulin secretion were measured...
December 7, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27917297/an-intrinsic-agonist-mechanism-for-activation-of-glucagon-like-peptide-1-receptor-by-its-extracellular-domain
#9
Yanting Yin, X Edward Zhou, Li Hou, Li-Hua Zhao, Bo Liu, Gaihong Wang, Yi Jiang, Karsten Melcher, H Eric Xu
The glucagon-like peptide-1 receptor is a class B G protein coupled receptor (GPCR) that plays key roles in glucose metabolism and is a major therapeutic target for diabetes. The classic two-domain model for class B GPCR activation proposes that the apo-state receptor is auto-inhibited by its extracellular domain, which physically interacts with the transmembrane domain. The binding of the C-terminus of the peptide hormone to the extracellular domain allows the N-terminus of the hormone to insert into the transmembrane domain to induce receptor activation...
2016: Cell Discovery
https://www.readbyqxmd.com/read/27915415/exendin-4-protects-huvecs-from-tunicamycin-induced-apoptosis-via-inhibiting-the-ire1a-jnk-caspase-3-pathway
#10
Li Wu, XiaoYing Liu, LinXi Wang, YanPing Wang, LiJing Wang, BinBin Guan, Zhou Chen, LiBin Liu
PURPOSE: The abnormal increase of apoptosis of endothelial cells induced by endoplasmic reticulum stress is a significant factor for vascular disease, especially for atherosclerosis. Protecting endothelial cells from endoplasmic reticulum stress is a crucial strategies to combate these diseases. The goal of this study was to explore the effect of Exendin-4, a glucagon-like peptide-1 receptor agonist, on tunicamycin-induced apoptosis in human umbilical vein endothelial cells. METHODS: All studies were performed in primary human umbilical vein endothelial cells treated with tunicamycin with or without Exendin-4 pretreatment...
December 3, 2016: Endocrine
https://www.readbyqxmd.com/read/27913661/effects-of-exendin-4-on-the-intrarenal-renin-angiotensin-system-and-interstitial-fibrosis-in-unilateral-ureteral-obstruction-mice-exendin-4-and-unilateral-ureteral-obstruction
#11
Ying Le, Zongji Zheng, Junyu Xue, Mengling Cheng, Meiping Guan, Yaoming Xue
OBJECTIVE: The objective of this article is to investigate the renoprotecive effects of exendin-4 in a mouse model of unilateral ureteral obstruction (UUO) and explore the putative mechanisms. METHODS: Male Balbc mice underwent sham operation or UUO surgery, and then received intraperitoneal injection of vehicle or exendin-4, respectively. After 14 days, mice were sacrificed and the left kidneys were collected and analyzed by histology, immunohistochemistry, Western blot, quantitative real-time reverse transcription polymerase chain reaction, radioimmunoassay and enzyme-linked immunosorbent assay...
October 2016: Journal of the Renin-angiotensin-aldosterone System: JRAAS
https://www.readbyqxmd.com/read/27908915/-the-hypothalamic-glucagon-like-peptide-1-glp-1-receptor-glp-1r-is-sufficient-but-not-necessary-for-the-regulation-of-energy-balance-and-glucose-homeostasis-in-mice
#12
Melissa A Burmeister, Jennifer E Ayala, Hannah Smouse, Adriana Landivar-Rocha, Jacob D Brown, Daniel J Drucker, Doris A Stoffers, Darleen A Sandoval, Randy J Seeley, Julio E Ayala
Pharmacological activation of the hypothalamic glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) promotes weight loss and improves glucose tolerance. This demonstrates that the hypothalamic GLP-1R is sufficient but does not show whether it is necessary for the effects of exogenous GLP-1R agonists (GLP-1RA) or endogenous GLP-1 on these parameters. To address this, we crossed mice harboring floxed Glp1r alleles to mice expressing Nkx2.1-Cre to knock down Glp1r expression throughout the hypothalamus (GLP-1RKD(ΔNkx2...
December 1, 2016: Diabetes
https://www.readbyqxmd.com/read/27907035/exendin-4-inhibits-hepatic-lipogenesis-by-increasing-%C3%AE-catenin-signaling
#13
Mi Hae Seo, Jinmi Lee, Seok-Woo Hong, Eun-Jung Rhee, Se Eun Park, Cheol Young Park, Ki Won Oh, Sung Woo Park, Won-Young Lee
The aim of this study is to investigate whether the beneficial effect of exendin-4 on hepatic steatosis is mediated by β-catenin signaling. After the HepG2 human hepatoma cells were treated with PA for 24 hours, total triglycerides levels were increased in a dose-dependent manner, and the expression levels of perilipin family members were upregulated in cells treated with 400 μM PA. For our in vitro model of hepatic steatosis, HepG2 cells were treated with 400 μM palmitic acid (PA) in the presence or absence of 100 nM exendin-4 for 24 hours...
2016: PloS One
https://www.readbyqxmd.com/read/27898108/monotreme-glucagon-like-peptide-1-in-venom-and-gut-one-gene-two-very-different-functions
#14
Enkhjargal Tsend-Ayush, Chuan He, Mark A Myers, Sof Andrikopoulos, Nicole Wong, Patrick M Sexton, Denise Wootten, Briony E Forbes, Frank Grutzner
The importance of Glucagon like peptide 1 (GLP-1) for metabolic control and insulin release sparked the evolution of genes mimicking GLP-1 action in venomous species (e.g. Exendin-4 in Heloderma suspectum (gila monster)). We discovered that platypus and echidna express a single GLP-1 peptide in both intestine and venom. Specific changes in GLP-1 of monotreme mammals result in resistance to DPP-4 cleavage which is also observed in the GLP-1 like Exendin-4 expressed in Heloderma venom. Remarkably we discovered that monotremes evolved an alternative mechanism to degrade GLP-1...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895384/exendin-4-induces-extracellular-superoxide-dismutase-through-histone-h3-acetylation-in-human-retinal-endothelial-cells
#15
Hiroyuki Yasuda, Atsuko Ohashi, Shohei Nishida, Tetsuro Kamiya, Tetsuya Suwa, Hirokazu Hara, Jun Takeda, Yoshinori Itoh, Tetsuo Adachi
Extracellular-superoxide dismutase (genetic name SOD3) is a secreted anti-oxidative enzyme, and its presence in vascular walls may play an important role in protecting the vascular system against oxidative stress. Oxidative stress has been implicated in the pathogenesis of diabetic retinopathy; therefore, increases in extracellular-superoxide dismutase have been suggested to inhibit the progression of diabetic retinopathy. Incretin-based drugs such as glucagon-like peptide-1 receptor agonists are used in the treatment of type 2 diabetes...
November 2016: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/27888738/oxyntomodulin-analog-and-exendin-4-derivative-lower-plasma-glucose-in-cattle
#16
S ThanThan, Y Asada, T Saito, K Ochiiwa, H Zhao, S W Naing, H Kuwayama
The present study was undertaken with the aim of examining whether and how exendin-4 (1-3) fragment, ie, Ex-4 (1-3) fragment, contributes to the regulation of glucose. An analog of oxyntomodulin (OXM) ([Gly(2), Glu(3)]-OXM), a glucagon analog ([Gly(2), Glu(3)]-glucagon), and two derivatives of Ex-4 (glucandin and [Gly(2), Glu(3)]-glucandin) were synthesized by substituting with Gly(2), Glu(3) at the N-terminuses of OXM and glucagon and/or by attaching Ex-4 (30-39) amide at the C-terminus of glucagon. Effects of these peptides on plasma insulin and glucose concentrations were investigated in cattle by conducting 3 in vivo experiments...
November 2, 2016: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/27882092/the-influence-of-exendin-4-intervention-on-obese-diabetic-mouse-blood-and-the-pancreatic-tissue-immune-microenvironment
#17
Jinshui He, Chaowei Lian, Yanling Fang, Jinzhi Wu, Huowang Zhou, Xiaoling Ye
The aim of the study was to determine the influence of exendin-4 intervention on non-obese diabetic (NOD) mouse blood and the pancreatic tissue immune microenvironment. A total of 40 clean NOD mice were used in the study and randomly divided into 4 groups (n=10/group). The first group was blank control group D with normal saline intervention, and with different doses of exendin, i.e.,-4 2, 4 and 8 µg/kg/day. The three remaining groups were: i) Low-dose group A; ii) medium-dose group B; and iii) high-dose group C...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27882091/exendin-4-antagonizes-a%C3%AE-1-42-induced-attenuation-of-spatial-learning-and-memory-ability
#18
Xiaohui Wang, Li Wang, Ruirui Jiang, Yunyun Xu, Xueling Zhao, Yang Li
β-amyloid protein (Aβ) accumulation in cerebral centers involved in cognition and memory is a pivotal pathological feature of Alzheimer's disease (AD). The onset process of type 2 diabetes mellitus (T2DM) has a number of similarities compared with AD. Thus, it is hypothesized that the pharmacological therapy employed for the treatment of T2DM may help to prevent and ameliorate the symptoms of AD. This study demonstrated that Exendin-4, which is a glucagon-like peptide-1 analogue which is used as a therapeutic drug for T2DM, markedly antagonized Aβ fragment-induced attenuation of spatial learning and memory ability, as indicated by a Morris water maze experiment...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27878229/glucagon-like-peptide-1-improves-insulin-resistance-in-vitro-through-anti-inflammation-of-macrophages
#19
C Guo, T Huang, A Chen, X Chen, L Wang, F Shen, X Gu
Glucagon-like peptide 1 (GLP-1), a kind of gut hormone, is used in the treatment of type 2 diabetes (T2D). Emerging evidence indicates that GLP-1 has anti-inflammatory activity. Chronic inflammation in the adipose tissue of obese individuals is a cause of insulin resistance and T2D. We hypothesized that GLP-1 analogue therapy in patients with T2D could suppress the inflammatory response of macrophages, and therefore inhibit insulin resistance. Our results showed that GLP-1 agonist (exendin-4) not only attenuated macrophage infiltration, but also inhibited the macrophage secretion of inflammatory cytokines including TNF-β, IL-6, and IL-1β...
November 21, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/27872157/exendin-4-increases-oxygen-consumption-and-thermogenic-gene-expression-in-muscle-cells
#20
Jin-Seung Choung, Young-Sun Lee, Hee-Sook Jun
Glucagon-like peptide-1 (GLP1) has many anti-diabetic actions and also increases energy expenditure in vivo. Since skeletal muscle is a major organ controlling energy metabolism, we investigated whether GLP1 can affect energy metabolism in muscle. We found that treatment of differentiated C2C12 cells with Exendin-4 (Ex-4), a GLP1 receptor agonist, reduced oleate:palmitate-induced lipid accumulation and triglyceride content compared with cells without Ex-4 treatment. When we examined the oxygen consumption rate (OCR), not only the basal OCR but also the OCR induced by oleate:palmitate addition was significantly increased in Ex-4-treated differentiated C2C12 cells, and this was inhibited by Exendin-9, a GLP1 receptor antagonist...
November 21, 2016: Journal of Molecular Endocrinology
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