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https://www.readbyqxmd.com/read/27928774/a-3d-printed-anatomical-pancreas-and-kidney-phantom-for-optimizing-spect-ct-reconstruction-settings-in-beta-cell-imaging-using-111-in-exendin
#1
Wietske Woliner-van der Weg, Laura N Deden, Antoi P W Meeuwis, Maaike Koenrades, Laura H C Peeters, Henny Kuipers, Geert Jan Laanstra, Martin Gotthardt, Cornelis H Slump, Eric P Visser
BACKGROUND: Quantitative single photon emission computed tomography (SPECT) is challenging, especially for pancreatic beta cell imaging with (111)In-exendin due to high uptake in the kidneys versus much lower uptake in the nearby pancreas. Therefore, we designed a three-dimensionally (3D) printed phantom representing the pancreas and kidneys to mimic the human situation in beta cell imaging. The phantom was used to assess the effect of different reconstruction settings on the quantification of the pancreas uptake for two different, commercially available software packages...
December 2016: EJNMMI Physics
https://www.readbyqxmd.com/read/27917297/an-intrinsic-agonist-mechanism-for-activation-of-glucagon-like-peptide-1-receptor-by-its-extracellular-domain
#2
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
#3
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
#4
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
#5
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
#6
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/27900077/selective-beneficial-cardiometabolic-effects-of-vertical-sleeve-gastrectomy-are-predominantly-mediated-through-glucagon-like-peptide-glp-1-in-zucker-diabetic-fatty-rats
#7
Sunil Kumar, Raymond Lau, Thomas Palaia, Christopher Hall, Jenny Lee, Keneth Hall, Collin E Brathwaite, Louis Ragolia
BACKGROUND: Glucagon-like peptide-1 (GLP-1) level was significantly increased post Vertical Sleeve Gastrectomy (VSG), an effect believed to contribute to its beneficial cardiometabolic effects. OBJECTIVE: To validate the beneficial GLP-1 mediated cardiometabolic effects post VSG using GLP-1 antagonist (exendin 9-39) in Zucker diabetic fatty rats. METHODS: Animals were divided into three (n = 5) groups: (i) sham, (ii) VSG, and (iii) VSG received exendin 9-39 (GLP-1 receptor antagonist)...
December 2016: Annals of Medicine and Surgery
https://www.readbyqxmd.com/read/27898108/monotreme-glucagon-like-peptide-1-in-venom-and-gut-one-gene-two-very-different-functions
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/27831938/synthesis-of-fe3o4-nickel-silicate-core-shell-nanoparticles-for-his-tagged-enzyme-immobilizing-agents
#15
Moo-Kwang Shin, Byunghoon Kang, Nam-Kyung Yoon, Myeong-Hoon Kim, Jisun Ki, Seungmin Han, Jung-Oh Ahn, Seungjoo Haam
Immobilizing enzymes on artificially fabricated carriers for their efficient use and easy removal from reactants has attracted enormous interest for decades. Specifically, binding platforms using inorganic nanoparticles have been widely explored because of the benefits of their large surface area, easy surface modification, and high stability in various pH and temperatures. Herein, we fabricated Fe3O4 encapsulated 'sea-urchin' shaped nickel-silicate nanoparticles with a facile synthetic route. The enzymes were then rapidly and easily immobilized with poly-histidine tags (His-tags) and nickel ion affinity...
December 9, 2016: Nanotechnology
https://www.readbyqxmd.com/read/27831640/influence-and-significance-of-intervening-diabetes-microrna-expression-profile-of-nod-mice-with-exendin-4
#16
J-S He, C-W Lian, Y-L Fang, J-Z Wu, X-L Ye, S-B Zhu
OBJECTIVE: To provide selectable microRNA for intervening diabetes mellitus diseases, NOD mice's expression of microRNA in pancreas tissues and blood under the exendin-4 intervention of was observed and the difference of microRNA target gene was screened. MATERIALS AND METHODS: Forty clean NOD mice were randomly divided into four groups (in each group, n = 10): One is blank control group D which is intervened with normal saline, and the other three groups were divided into low-dose group A, middle-dose group B, and high-dose group C according to the different exendin-4 dosage 2, 4, and 8 μg/kg·d...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27826714/exendin-4-promotes-pancreatic-%C3%AE-cell-proliferation-via-inhibiting-the-expression-of-wnt5a
#17
Xinger Wu, Weiwei Liang, Hongyu Guan, Juan Liu, Liehua Liu, Hai Li, Xiaoying He, Jing Zheng, Jie Chen, Xiaopei Cao, Yanbing Li
Exendin-4, a glucagon-like peptide-1 receptor agonist, is currently regarded as an effective therapeutic strategy for type-2 diabetes. Previous studies indicated that exendin-4 promoted β cell proliferation. However, the underlying mechanisms remain largely unknown. Recently it was reported that exendin-4 promoted pancreatic β cell proliferation by regulating the expression level of Wnt4. The present study was designed to investigate whether other Wnt isoforms take part in accommodation of β-cell proliferation...
November 9, 2016: Endocrine
https://www.readbyqxmd.com/read/27823935/glucose-enhances-rat-islet-function-via-stimulating-cart-expression
#18
Wan Xu, Yuqing Zhang, Mengyao Bai, Feiye Zhou, Ruyuan Deng, Xueying Ji, Juan Zhang, Yun Liu, Libin Zhou, Xiao Wang
Cocaine- and amphetamine-regulated transcript (CART) is an anorexigenic peptide widely expressed in the central and peripheral nervous systems, as well as in endocrine cells. CART is markedly upregulated in the β-cells of several rodent models of type-2 diabetes. The stimulatory effect of exogenous CART peptide on insulin secretion is cAMP dependent. Glucose is the most important regulator of islet function. However, the role of CART in glucose-potentiated insulin secretion remains unclear. Here, our results showed that glucose time- and dose-dependently elicited CART mRNA expression in rat islets...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27819034/quantification-of-%C3%AE-cell-mass-in-intramuscular-islet-grafts-using-radiolabeled-exendin-4
#19
Daniel Espes, Ramkumar Selvaraju, Irina Velikyan, Martin Krajcovic, Per-Ola Carlsson, Olof Eriksson
BACKGROUND: There is an increasing interest in alternative implantation sites to the liver for islet transplantation. Intramuscular implantation has even been tested clinically. Possibilities to monitor β-cell mass would be of huge importance not only for the understanding of islet engraftment but also for the decision of changing the immunosuppressive regime. We have therefore evaluated the feasibility of quantifying intramuscular β-cell mass using the radiolabeled glucagon like peptide-1 receptor agonist DO3A-VS-Cys(40)-Exendin-4...
August 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27797911/novel-monoclonal-antibody-is-an-allosteric-insulin-receptor-antagonist-that-induces-insulin-resistance
#20
Anne M Cieniewicz, Thomas Kirchner, Simon A Hinke, Rupesh Nanjunda, Katharine D'Aquino, Ken Boayke, Philip R Cooper, Robert Perkinson, Mark L Chiu, Dana L Johnson, Jean M Whaley, Eilyn R Lacy, Russell B Lingham, Yin Liang, Anthony J Kihm
A hallmark of type 2 diabetes is impaired insulin receptor signaling resulting in dysregulation of glucose homeostasis. Understanding the molecular origins and progression of diabetes and developing therapeutics are dependent on experimental models of hyperglycemia, hyperinsulinemia and insulin resistance. Here, we present a novel monoclonal antibody, IRAB-B, a specific, potent insulin receptor antagonist that creates rapid and long lasting insulin resistance. IRAB-B binds to the insulin receptor with nanomolar affinity, and in the presence of insulin, efficiently blocks receptor phosphorylation within minutes and is sustained for at least 3 days in vitro...
October 26, 2016: Diabetes
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