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https://www.readbyqxmd.com/read/29045658/exendin-4-a-glucagon-like-peptide-1-receptor-agonist-attenuates-breast-cancer-growth-by-inhibiting-nf-%C3%AE%C2%BAb-activation
#1
Chikayo Iwaya, Takashi Nomiyama, Shiho Komatsu, Takako Kawanami, Yoko Tsutsumi, Yuriko Hamaguchi, Tsuyoshi Horikawa, Yasuteru Yoshinaga, Shinichi Yamashita, Tomoko Tanaka, Yuichi Terawaki, Makito Tanabe, Kazuki Nabeshima, Akinori Iwasaki, Toshihiko Yanase
Incretin therapies have received significant attention because of their tissue-protective effects, which extend beyond those associated with glycemic control. Cancer is a primary cause of death in patients with diabetes mellitus. We previously reported anti-prostate cancer effects of the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonist exendin-4 (Ex-4). Breast cancer is one of the most common cancers in female patients with type 2 diabetes mellitus and obesity. Thus, we examined whether GLP-1 action could attenuate breast cancer...
October 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/29031718/g%C3%AE-s-regulates-glucagon-like-peptide-1-receptor-mediated-cyclic-amp-generation-at%C3%A2-rab5-endosomal-compartment
#2
Shravan Babu Girada, Ramya S Kuna, Shilpak Bele, Zhimeng Zhu, N R Chakravarthi, Richard D DiMarchi, Prasenjit Mitra
OBJECTIVE: Upon activation, G protein coupled receptors (GPCRs) associate with heterotrimeric G proteins at the plasma membrane to initiate second messenger signaling. Subsequently, the activated receptor experiences desensitization, internalization, and recycling back to the plasma membrane, or it undergoes lysosomal degradation. Recent reports highlight specific cases of persistent cyclic AMP generation by internalized GPCRs, although the functional significance and mechanistic details remain to be defined...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29022064/proinflammatory-switch-from-g%C3%AE-s-to-g%C3%AE-i-signaling-by-glucagon-like-peptide-1-receptor-in-murine-splenic-monocyte-following-burn-injury
#3
Qing-Hong Zhang, Ji-Wei Hao, Guang-Lei Li, Xiao-Jing Ji, Xu-Dong Yao, Ning Dong, Yong-Ming Yao
OBJECTIVE: Glucagon-like peptide-1 (GLP-1)-based therapy via G protein-coupled receptor (GPCR) GLP-1R, to attenuate hyperglycemia in critical care has attracted great attention. However, the exaggerated inflammation by GLP-1R agonist, Exendin-4, in a mouse model of burn injury was quite unexpected. Recent studies found that GPCR might elicit proinflammatory effects by switching from Gαs to Gαi signaling in the immune system. Thus, we aimed to investigate the possible Gαs to Gαi switch in GLP-1R signaling in monocyte following burn injury...
October 11, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28991675/sodium-butyrate-exerts-protective-effect-against-parkinson-s-disease-in-mice-via-stimulation-of-glucagon-like-peptide-1
#4
Jiaming Liu, Fangyan Wang, Suzhi Liu, Jimei Du, Xuezhen Hu, Jiaojiao Xiong, Renchi Fang, Wenqian Chen, Jing Sun
Sodium butyrate (NaB) has exhibited protective activity in neurological disorders. Here, we investigated the neuroprotective effect and potential mechanisms of NaB in a mouse model of Parkinson's disease (PD). A mouse was intraperitoneally treated with MPTP (30mg/kg) for 7 consecutive days to induce PD model and NaB (200mg/kg) was intragastrically treated for 3weeks. The behavioral tests were then conducted. Dopaminergic degeneration was evaluated by western blot and immunohistochemistry of tyrosine hydroxylase (TH) in the SN...
October 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28986282/exendin-4-attenuates-neuronal-death-via-glp-1r-pi3k-akt-pathway-in-early-brain-injury-after-subarachnoid-hemorrhage-in-rats
#5
Zhiyi Xie, Budbazar Enkhjargal, Lingyun Wu, Keren Zhou, Chengmei Sun, Xin Hu, Vadim Gospodarev, Jiping Tang, Chao You, John H Zhang
Neuronal apoptosis is considered to be a crucial therapeutic target against early brain injury (EBI) after subarachnoid hemorrhage (SAH). Emerging evidence indicates that Exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, plays a neuroprotective role in cerebrovascular disease. This study was conducted in order to verify the neuroprotective role of EX-4 in EBI after SAH in rats. The endovascular perforation model of SAH was performed in Sprague-Dawley rats (n = 153). Ex-4 was intraperitoneally injected 1 h after SAH induction in the rats (SAH + Ex-4)...
October 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28969637/the-role-of-endothelial-nitric-oxide-in-the-anti-restenotic-effects-of-liraglutide-in-a-mouse-model-of-restenosis
#6
Hideki Kushima, Yusaku Mori, Masakazu Koshibu, Munenori Hiromura, Kyoko Kohashi, Michishige Terasaki, Tomoyasu Fukui, Tsutomu Hirano
BACKGROUND: Previous animal studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1RAs) suppress arterial restenosis, a major complication of angioplasty, presumably through their direct action on vascular smooth muscle cells. However, the contribution of vascular endothelial cells (VECs) to this process remains unknown. In addition, the potential interference caused by severe hyperglycemia and optimal treatment regimen remain to be determined. METHODS: Nine-week-old male C57BL6 (wild-type) and diabetic db/db mice were randomly divided into vehicle or liraglutide treatment groups (Day 1), and subject to femoral artery wire injuries (Day 3)...
October 2, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28953210/99mtc-exendin-9-39-octreotide-biokinetics-and-radiation-dosimetry-in-healthy-individuals
#7
Blanca E Ocampo-García, Clara L Santos-Cuevas, Myrna A Luna-Gutiérrez, Eleazar Ignacio-Alvarez, Martha Pedraza-López, Cesar Manzano-Mayoral
AIM: About 90% of insulinomas are benign and 5-15% are malignant. Benign insulinomas express the glucagon-like peptide-1 receptor (GLP-1R, which recognizes exendin-4 and low levels of the somatostatin receptor (SSTR, which recognizes octreotide), whereas malignant insulinomas overexpress SSTR and low levels of GLP-1R. Recently, Lys(Tc-EDDA/HYNIC)-exendin(9-39)/Tc-EDDA/HYNIC-Tyr-octreotide was formulated to detect 100% of insulinomas. The aim of this study was to estimate the biokinetics and dosimetry of Tc-exendin(9-39)/octreotide in four healthy individuals...
November 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/28947828/fenugreek-compound-n55-lowers-plasma-glucose-through-the-enhancement-of-response-of-physiological-glucagon-like-peptide-1
#8
I-Wen Chou, Yu-Hong Cheng, Yet-Ran Chen, Patrick Ching-Ho Hsieh, Klim King
Glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) analogues are approved for treating type 2 diabetes, but are known to activate GLP-1R signaling globally and constitutively. Active compound N55, previously isolated from fenugreek, enhances the potency of GLP-1 without activating GLP-1R. Here we investigated if N55 lowers plasma glucose base on physiological levels of GLP-1. N55 was found to dose-dependently lower plasma glucose in non-fasted mice but not in the fasted mice, with the effect attenuated by GLP-1R antagonist exendin-(9-39) (Ex-9)...
September 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28932183/plant-polyphenols-and-exendin-4-prevent-hyperactivity-and-tnf-%C3%AE-release-in-lps-treated-in-vitro-neuron-astrocyte-microglial-networks
#9
Francesca Gullo, Michela Ceriani, Alessia D'Aloia, Enzo Wanke, Andrew Constanti, Barbara Costa, Marzia Lecchi
Increasing evidence supports a decisive role for neuroinflammation in the neurodegenerative process of several central nervous system (CNS) disorders. Microglia are essential mediators of neuroinflammation and can regulate a broad spectrum of cellular responses by releasing reactive oxygen intermediates, nitric oxide, proteases, excitatory amino acids, and cytokines. We have recently shown that also in ex-vivo cortical networks of neurons, astrocytes and microglia, an increased level of tumor necrosis factor-alpha (TNF-α) was detected a few hours after exposure to the bacterial endotoxin lipopolysaccharide (LPS)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28920919/age-dependent-human-%C3%AE-cell-proliferation-induced-by-glucagon-like-peptide-1-and-calcineurin-signaling
#10
Chunhua Dai, Yan Hang, Alena Shostak, Greg Poffenberger, Nathaniel Hart, Nripesh Prasad, Neil Phillips, Shawn E Levy, Dale L Greiner, Leonard D Shultz, Rita Bottino, Seung K Kim, Alvin C Powers
Inadequate pancreatic β cell function underlies type 1 and type 2 diabetes mellitus. Strategies to expand functional cells have focused on discovering and controlling mechanisms that limit the proliferation of human β cells. Here, we developed an engraftment strategy to examine age-associated human islet cell replication competence and reveal mechanisms underlying age-dependent decline of β cell proliferation in human islets. We found that exendin-4 (Ex-4), an agonist of the glucagon-like peptide 1 receptor (GLP-1R), stimulates human β cell proliferation in juvenile but not adult islets...
October 2, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28920591/glucagon-like-peptide-1-receptor-signaling-in-the-lateral-dorsal-tegmental-nucleus-regulates-energy-balance
#11
David J Reiner, Rosa M Leon, Lauren E McGrath, Kieran Koch-Laskowski, Joel D Hahn, Scott E Kanoski, Elizabeth G Mietlicki-Baase, Matthew R Hayes
The neurobiological substrates that mediate the anorectic effects of both endogenous glucagon-like peptide-1 (GLP-1) and exogenous GLP-1 receptor (GLP-1R) agonists are an active area of investigation. As the lateral dorsal tegmental nucleus (LDTg) expresses the GLP-1R and represents a potential neuroanatomical hub connecting the nucleus tractus soliartius (NTS), the major central source of GLP-1, with the other nuclei in the midbrain and forebrain, we tested the hypothesis that GLP-1R signaling in the LDTg controls food intake...
September 18, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28919123/liraglutide-a-glucagon-like-peptide-1-receptor-agonist-facilitates-osteogenic-proliferation-and-differentiation-in-mc3t3-e1-cells-through-phosphoinositide-3-kinase-pi3k-protein-kinase-b-akt-extracellular-signal-related-kinase-erk-1-2-and-camp-protein-kinase
#12
Xuelun Wu, Shilun Li, Peng Xue, Yukun Li
Previous studies have proven that glucagon-like peptide-1 (GLP-1) and its receptor agonist exert favorable anabolic effects on skeletal metabolism. However, whether GLP-1 could directly impact osteoblast-mediated bone formation is still controversial, and the underlying molecular mechanism remains to be elucidated. Thus in this paper, we investigated the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, on murine MC3T3-E1 preosteoblasts proliferation and differentiation and explored the potential cellular basis...
September 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28912645/anti-inflammatory-effect-of-glucagon-like-peptide-1-receptor-agonist-exendin-4-through-modulation-of-ib1-jip1-expression-and-jnk-signaling-in-stroke
#13
Soojin Kim, Jaewon Jeong, Hye-Seon Jung, Bokyung Kim, Ye-Eun Kim, Da-Sol Lim, So-Dam Kim, Yun Seon Song
Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28894301/lateral-hypothalamic-glp-1-receptors-are-critical-for-the-control-of-food-reinforcement-ingestive-behavior-and-body-weight
#14
L López-Ferreras, J E Richard, E E Noble, K Eerola, R H Anderberg, K Olandersson, L Taing, S E Kanoski, M R Hayes, K P Skibicka
Increased motivation for highly rewarding food is a major contributing factor to obesity. Most of the literature focuses on the mesolimbic nuclei as the core of reward behavior regulation. However, the lateral hypothalamus (LH) is also a key reward-control locus in the brain. Here we hypothesize that manipulating glucagon-like peptide-1 receptor (GLP-1R) activity selectively in the LH can profoundly affect food reward behavior, ultimately leading to obesity. Progressive ratio operant responding for sucrose was examined in male and female rats, following GLP-1R activation and pharmacological or genetic GLP-1R blockade in the LH...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28891030/species-differences-in-pancreatic-binding-of-do3a-vs-cys-40-exendin4
#15
Olof Eriksson, Ulrika Rosenström, Ram K Selvaraju, Barbro Eriksson, Irina Velikyan
AIMS: Radiolabeled Exendin-4 has been proposed as suitable imaging marker for pancreatic beta cell mass quantification mediated by Glucagon-like peptide-1 receptor (GLP-1R). However, noticeable species variations in basal pancreatic uptake as well as uptake reduction degree due to selective beta cell ablation were observed. METHODS: In vitro and ex vivo autoradiography studies of pancreas were performed using [(177)Lu]Lu-DO3A-VS-Cys(40)-Exendin4, in order to investigate the mechanism of uptake as well as the islet uptake contrast in mouse, rat, pig, and non-human primate...
November 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28876923/spirohexene-tetrazine-ligation-enables-bioorthogonal-labeling-of-class-b-g-protein-coupled-receptors-in-live-cells
#16
Carlo P Ramil, Maoqing Dong, Peng An, Tracey M Lewandowski, Zhipeng Yu, Laurence J Miller, Qing Lin
A new bioorthogonal reactant pair, spiro[2.3]hex-1-ene (Sph) and 3,6-di(2-pyridyl)-s-tetrazine (DpTz), for the strain-promoted inverse electron-demand Diels-Alder cycloaddition, that is, tetrazine ligation, is reported. As compared to the previously reported strained alkenes such as trans-cyclooctene (TCO) and 1,3-disubstituted cyclopropene, Sph exhibits balanced reactivity and stability in tetrazine ligation with the protein substrates. A lysine derivative of Sph, SphK, was site-selectively incorporated into the extracellular loop regions (ECLs) of GCGR and GLP-1R, two members of class B G protein-coupled receptors (GPCRs) in mammalian cells with the incorporation efficiency dependent on the location...
September 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28874313/new-therapeutic-perspectives-in-non-alcoholic-steatohepatitis
#17
Javier Ampuero, Yolanda Sánchez-Torrijos, Virginia Aguilera, Francisco Bellido, Manuel Romero-Gómez
Management of non-alcoholic steatohepatitis is focused on restitution of metabolic derangement, weight loss and drugs able to improve steatosis, ballooning and fibrosis. Life-style interventions based on Mediterranean diet and increasing physical activity are the first line therapy. In patients with unsuccessful life-style intervention several drugs are under development: agonist PPAR, agonist GLP-1R and agonist FXR together with drugs focussing on inflammation, ballooning, apoptosis and fibrosis. Bariatric surgery or advanced endoscopy are reserved for morbid obese without response to life-style intervention and weighting loss drugs...
September 2, 2017: Gastroenterología y Hepatología
https://www.readbyqxmd.com/read/28867303/treatment-with-a-glp-1r-agonist-over-four-weeks-promotes-weight-loss-moderated-changes-in-frontal-striatal-brain-structures-in-individuals-with-mood-disorders
#18
Rodrigo B Mansur, Andre Zugman, Juhie Ahmed, Danielle S Cha, Mehala Subramaniapillai, Yena Lee, Julie Lovshin, Jung G Lee, Jae-Hon Lee, Vladislav Drobinin, Jason Newport, Elisa Brietzke, Eva Z Reininghaus, Kang Sim, Maj Vinberg, Natalie Rasgon, Tomas Hajek, Roger S McIntyre
Cognitive deficits are a core feature across psychiatric disorders. Emerging evidence indicates that metabolic pathways are highly relevant for the substrates and phenomenology of the cognitive domain. Herein, we aimed to determine the effects of liraglutide, a GLP-1R agonist, on brain structural/volumetric parameters in adults with a mood disorder. This is the secondary analysis of a 4-week, pilot, proof-of-concept, open-label study. Participants (N=19) exhibiting impairments in executive function with either major depressive disorder (MDD) or bipolar disorder (BD) were recruited...
August 31, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28855317/novel-skeletal-effects-of-glucagon-like-peptide-1-glp-1-receptor-agonists
#19
Guillaume Mabilleau, Marie Pereira, Chantal Chenu
Type 2 diabetes mellitus (T2DM) leads to bone fragility and predisposes to increased risk of fracture, poor bone healing and other skeletal complications. In addition, some anti-diabetic therapies for T2DM can have notable detrimental skeletal effects. Thus an appropriate therapeutic strategy for T2DM should not only be effective in re-establishing good glycaemic control but also in minimising skeletal complications. There is increasing evidence that Glucagon-like peptide-1 receptor (GLP-1r) agonists, now greatly prescribed for the treatment of T2DM, have beneficial skeletal effects although the underlying mechanisms are not completely understood...
August 30, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28846606/the-emerging-role-of-glp-1-receptors-in-dna-repair-implications-in-neurological-disorders
#20
REVIEW
Jenq-Lin Yang, Wei-Yu Chen, Shang-Der Chen
Glucagon-like peptide-1 (GLP-1) is originally found as a metabolic hormone (incretin) that is able to regulate blood-glucose levels via promoting synthesis and secretion of insulin. GLP-1 and many analogues are approved for treatment of type II diabetes. Accumulating results imply that GLP-1 performs multiple functions in various tissues and organs beyond regulation of blood-glucose. The neuroprotective function of GLP-1 has been extensively explored during the past two decades. Three of our previous studies have shown that apurinic/apyrimidinic endonuclease 1 (APE1) is the only protein of the base excision repair (BER) pathway able to be regulated by oxidative stress or exogenous stimulations in rat primary cortical neurons...
August 26, 2017: International Journal of Molecular Sciences
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