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https://www.readbyqxmd.com/read/28270438/menin-and-prmt5-suppress-glp1-receptor-transcript-and-pka-mediated-phosphorylation-of-foxo1-and-creb
#1
Abdul Bari Muhammad, Bowen Xing, Chengyang Liu, Ali Naji, Xiaosong Ma, Rebecca A Simmons, Xianxin Hua
Menin is a scaffold protein that interacts with several epigenetic mediators to regulate gene transcription, and suppresses pancreatic beta cell proliferation. Tamoxifen inducible deletion of multiple endocrine neoplasia type 1 (MEN1) gene, which encodes the protein menin, increases beta cell mass in multiple murine models of diabetes and ameliorates diabetes. Glucagon-like-peptide-1 (GLP1) is another key physiological modulator of beta cell mass and glucose homeostasis. However, it is not clearly understood whether menin crosstalks with GLP1 signaling...
March 7, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28144621/glp-1r-signaling-directly-activates-arcuate-nucleus-kisspeptin-action-in-brain-slices-but-does-not-rescue-luteinizing-hormone-inhibition-in-ovariectomized-mice-during-negative-energy-balance
#2
Kristy M Heppner, Arian F Baquero, Camdin M Bennett, Sarah R Lindsley, Melissa A Kirigiti, Baylin Bennett, Martha A Bosch, Aaron J Mercer, Oline K Rønnekleiv, Cadence True, Kevin L Grove, M Susan Smith
Kisspeptin (Kiss1) neurons in the hypothalamic arcuate nucleus (ARC) are key components of the hypothalamic-pituitary-gonadal axis, as they regulate the basal pulsatile release of gonadotropin releasing hormone (GnRH). ARC Kiss1 action is dependent on energy status, and unmasking metabolic factors responsible for modulating ARC Kiss1 neurons is of great importance. One possible factor is glucagon-like peptide 1 (GLP-1), an anorexigenic neuropeptide produced by brainstem preproglucagon neurons. Because GLP fiber projections and the GLP-1 receptor (GLP-1R) are abundant in the ARC, we hypothesized that GLP-1R signaling could modulate ARC Kiss1 action...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28097390/a-role-of-plc-pkc-dependent-pathway-in-glp-1-stimulated-insulin-secretion
#3
REVIEW
Makoto Shigeto, Chae Young Cha, Patrik Rorsman, Kohei Kaku
Glucagon-like peptide-1 (GLP-1) is an endogenous glucose-lowering hormone and GLP-1 receptor agonists are currently being used as antidiabetic drugs clinically. The canonical signalling pathway (including cAMP, Epac2, protein kinase A (PKA) and KATP channels) is almost universally accepted as the main mechanism of GLP-1-stimulated insulin secretion. This belief is based on in vitro studies that used nanomolar (1-100 nM) concentrations of GLP-1. Recently, it was found that the physiological concentrations (1-10 pM) of GLP-1 also stimulate insulin secretion from isolated islets, induce membrane depolarization and increase of intracellular [Ca(2+)] in isolated β cells/pancreatic islets...
January 17, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28053040/disruption-of-glucagon-like-peptide-1-signaling-in-sim1-neurons-reduces-physiological-and-behavioral-reactivity-to-acute-and-chronic-stress
#4
Sriparna Ghosal, Amy E B Packard, Parinaz Mahbod, Jessica M McKlveen, Randy J Seeley, Brent Myers, Yvonne Ulrich-Lai, Eric P Smith, David A D'Alessio, James P Herman
Organismal stress initiates a tightly orchestrated set of responses involving complex physiological and neurocognitive systems. Here, we present evidence for glucagon-like peptide 1 (GLP-1)-mediated paraventricular hypothalamic circuit coordinating the global stress response. The GLP-1 receptor (Glp1r) in mice was knocked down in neurons expressing single-minded 1, a transcription factor abundantly expressed in the paraventricular nucleus (PVN) of the hypothalamus. Mice with single-minded 1-mediated Glp1r knockdown had reduced hypothalamic-pituitary-adrenal axis responses to both acute and chronic stress and were protected against weight loss associated with chronic stress...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27917862/purslane-portulaca-oleracea-seed-consumption-and-aerobic-training-improves-biomarkers-associated-with-atherosclerosis-in-women-with-type-2-diabetes-t2d
#5
Firouzeh Dehghan, Rahman Soori, Khadijeh Gholami, Mitra Abolmaesoomi, Ashril Yusof, Sekaran Muniandy, Sara Heidarzadeh, Parvin Farzanegi, Mohammad Ali Azarbayjani
The aim of this study was to investigate the responses of atherosclerosis plaque biomarkers to purslane seed consumption and aerobic training in women with T2D. 196 women with T2D were assigned into; (1) placebo (PL), (2) aerobic training+placebo (AT + PL), 3) purslane seeds (PS), aerobic training+purslane seeds (AT + PS). The training program and purslane seeds consumption (2.5 g lunch and 5 g dinner) were carried out for 16 weeks. The components of purslane seed were identified and quantified by GC-MS...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27908915/the-hypothalamic-glucagon-like-peptide-1-receptor-is-sufficient-but-not-necessary-for-the-regulation-of-energy-balance-and-glucose-homeostasis-in-mice
#6
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...
February 2017: Diabetes
https://www.readbyqxmd.com/read/27858848/a-genetic-variant-in-glp1r-is-associated-with-response-to-dpp-4-inhibitors-in-patients-with-type-2-diabetes
#7
Eugene Han, Hye Sun Park, Obin Kwon, Eun Yeong Choe, Hye Jin Wang, Yong-Ho Lee, Sang-Hak Lee, Chul Hoon Kim, Lee-Kyung Kim, Soo Heon Kwak, Kyong Soo Park, Chul Sik Kim, Eun Seok Kang
Incretin hormone-based therapy in type 2 diabetes has been widely used, and dipepdityl peptidase-4 (DPP-4) inhibitors, which prevent incretin degradation, have become popular oral hypoglycemic agents. The efficacy of DPP-4 inhibitors varies from individuals, and factors determining responses to DPP-4 inhibitors have not been fully established. We aimed to investigate whether genetic variations in glucagon-like peptide (GLP-1) receptor are associated with responses to DPP-4 inhibitors in patients with type 2 diabetes...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27810935/disruption-of-glucagon-like-peptide-1-signaling-in-sim1-neurons-reduces-physiological-and-behavioral-reactivity-to-acute-and-chronic-stress
#8
Sriparna Ghosal, Amy E B Packard, Parinaz Mahbod, Jessica M McKlveen, Randy J Seeley, Brent Myers, Yvonne Ulrich-Lai, Eric P Smith, David A D'Alessio, James P Herman
Organismal stress initiates a tightly orchestrated set of responses involving complex physiological and neurocognitive systems. Here, we present evidence for glucagon-like peptide 1 (GLP-1) mediated paraventricular hypothalamic circuit coordinating the global stress response. The GLP-1 receptor (Glp1r) in mice was knocked down in neurons expressing single-minded 1 (Sim1), a transcription factor abundantly expressed in the paraventricular nucleus (PVN) of the hypothalamus. Mice with Sim1-mediated Glp1r knockdown had reduced hypothalamic-pituitary-adrenal (HPA) axis responses to both acute and chronic stress and were protected against weight loss associated with chronic stress...
November 3, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27677765/metabolic-effects-of-orally-administered-small-molecule-agonists-of-gpr55-and-gpr119-in-multiple-low-dose-streptozotocin-induced-diabetic-and-incretin-receptor-knockout-mice
#9
Aine M McKillop, Brian M Moran, Yasser H A Abdel-Wahab, Noella M Gormley, Peter R Flatt
AIMS/HYPOTHESIS: Abnormal cannabidiol (Abn-CBD) and AS-1269574 are potent selective agonists for GPR55 and GPR119, respectively. The present study evaluated the actions and ability of these small-molecule agonists to counteract experimental diabetes in mice. METHODS: Diabetes was induced in NIH Swiss mice by five consecutive daily intraperitoneal injections of 40 mg/(kg body weight) streptozotocin. Diabetic mice received daily oral administration of Abn-CBD or AS-1269574 (0...
September 27, 2016: Diabetologia
https://www.readbyqxmd.com/read/27624071/aurora-kinase-a-overexpression-in-mouse-mammary-epithelium-induces-mammary-adenocarcinomas-harboring-genetic-alterations-shared-with-human-breast-cancer
#10
Warapen Treekitkarnmongkol, Hiroshi Katayama, Kazuharu Kai, Kaori Sasai, Jennifer Carter Jones, Jing Wang, Li Shen, Aysegul A Sahin, Mihai Gagea, Naoto T Ueno, Chad J Creighton, Subrata Sen
Recent data from The Cancer Genome Atlas analysis have revealed that Aurora kinase A (AURKA) amplification and overexpression characterize a distinct subset of human tumors across multiple cancer types. Although elevated expression of AURKA has been shown to induce oncogenic phenotypes in cells in vitro, findings from transgenic mouse models of Aurora-A overexpression in mammary glands have been distinct depending on the models generated. In the present study, we report that prolonged overexpression of AURKA transgene in mammary epithelium driven by ovine β-lactoglobulin promoter, activated through multiple pregnancy and lactation cycles, results in the development of mammary adenocarcinomas with alterations in cancer-relevant genes and epithelial-to-mesenchymal transition...
December 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27475229/stromal-cell-derived-factor-1-is-upregulated-by%C3%A2-dipeptidyl-peptidase-4-inhibition-and-has%C3%A2-protective-roles-in-progressive-diabetic%C3%A2-nephropathy
#11
Satoru Takashima, Hiroki Fujita, Hiromi Fujishima, Tatsunori Shimizu, Takehiro Sato, Tsukasa Morii, Katsushi Tsukiyama, Takuma Narita, Takamune Takahashi, Daniel J Drucker, Yutaka Seino, Yuichiro Yamada
The role of stromal cell-derived factor-1 (SDF-1) in the pathogenesis of diabetic nephropathy and its modification by dipeptidyl peptidase-4 (DPP-4) inhibition are uncertain. Therefore, we studied this independent of glucagon-like peptide-1 receptor (GLP-1R) signaling using two Akita diabetic mouse models, the diabetic-resistant C57BL/6-Akita and diabetic-prone KK/Ta-Akita. Increased SDF-1 expression was found in glomerular podocytes and distal nephrons in the diabetic-prone mice, but not in kidneys from diabetic-resistant mice...
October 2016: Kidney International
https://www.readbyqxmd.com/read/27460695/vascular-effects-of-linagliptin-in-non-obese-diabetic-mice-are-glucose-independent-and-involve-positive-modulation-of-the-endothelial-nitric-oxide-synthase-enos-caveolin-1-cav-1-pathway
#12
Valentina Vellecco, Emma Mitidieri, Antonella Gargiulo, Vincenzo Brancaleone, Danilo Matassa, Thomas Klein, Franca Esposito, Giuseppe Cirino, Mariarosaria Bucci
AIM: To test the effect of linagliptin in non-obese diabetic (NOD) mice, a murine model of type 1 diabetes, to unveil a possible direct cardiovascular action of dipeptidyl peptidase 4 (DPP-4) inhibitors beyond glycaemia control. METHODS: NOD mice were grouped according to glycosuria levels as NODI: none; NODII: high; NODIII: severe. Linagliptin treatment was initiated once they reached NODII levels. Vascular reactivity was assessed ex vivo on aorta harvested from mice upon reaching NODIII level...
December 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27310434/pharmacogenetics-genetic-approach-supports-cardiovascular-safety-of-glp1r-agonists
#13
Irene Fernández-Ruiz
No abstract text is available yet for this article.
August 2016: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/27252175/a-genomic-approach-to-therapeutic-target-validation-identifies-a-glucose-lowering-glp1r-variant-protective-for-coronary-heart-disease
#14
Robert A Scott, Daniel F Freitag, Li Li, Audrey Y Chu, Praveen Surendran, Robin Young, Niels Grarup, Alena Stancáková, Yuning Chen, Tibor V Varga, Hanieh Yaghootkar, Jian'an Luan, Jing Hua Zhao, Sara M Willems, Jennifer Wessel, Shuai Wang, Nisa Maruthur, Kyriaki Michailidou, Ailith Pirie, Sven J van der Lee, Christopher Gillson, Ali Amin Al Olama, Philippe Amouyel, Larraitz Arriola, Dominique Arveiler, Iciar Aviles-Olmos, Beverley Balkau, Aurelio Barricarte, Inês Barroso, Sara Benlloch Garcia, Joshua C Bis, Stefan Blankenberg, Michael Boehnke, Heiner Boeing, Eric Boerwinkle, Ingrid B Borecki, Jette Bork-Jensen, Sarah Bowden, Carlos Caldas, Muriel Caslake, L Adrienne Cupples, Carlos Cruchaga, Jacek Czajkowski, Marcel den Hoed, Janet A Dunn, Helena M Earl, Georg B Ehret, Ele Ferrannini, Jean Ferrieres, Thomas Foltynie, Ian Ford, Nita G Forouhi, Francesco Gianfagna, Carlos Gonzalez, Sara Grioni, Louise Hiller, Jan-Håkan Jansson, Marit E Jørgensen, J Wouter Jukema, Rudolf Kaaks, Frank Kee, Nicola D Kerrison, Timothy J Key, Jukka Kontto, Zsofia Kote-Jarai, Aldi T Kraja, Kari Kuulasmaa, Johanna Kuusisto, Allan Linneberg, Chunyu Liu, Gaëlle Marenne, Karen L Mohlke, Andrew P Morris, Kenneth Muir, Martina Müller-Nurasyid, Patricia B Munroe, Carmen Navarro, Sune F Nielsen, Peter M Nilsson, Børge G Nordestgaard, Chris J Packard, Domenico Palli, Salvatore Panico, Gina M Peloso, Markus Perola, Annette Peters, Christopher J Poole, J Ramón Quirós, Olov Rolandsson, Carlotta Sacerdote, Veikko Salomaa, María-José Sánchez, Naveed Sattar, Stephen J Sharp, Rebecca Sims, Nadia Slimani, Jennifer A Smith, Deborah J Thompson, Stella Trompet, Rosario Tumino, Daphne L van der A, Yvonne T van der Schouw, Jarmo Virtamo, Mark Walker, Klaudia Walter, Jean E Abraham, Laufey T Amundadottir, Jennifer L Aponte, Adam S Butterworth, Josée Dupuis, Douglas F Easton, Rosalind A Eeles, Jeanette Erdmann, Paul W Franks, Timothy M Frayling, Torben Hansen, Joanna M M Howson, Torben Jørgensen, Jaspal Kooner, Markku Laakso, Claudia Langenberg, Mark I McCarthy, James S Pankow, Oluf Pedersen, Elio Riboli, Jerome I Rotter, Danish Saleheen, Nilesh J Samani, Heribert Schunkert, Peter Vollenweider, Stephen O'Rahilly, Panos Deloukas, John Danesh, Mark O Goodarzi, Sekar Kathiresan, James B Meigs, Margaret G Ehm, Nicholas J Wareham, Dawn M Waterworth
Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia...
June 1, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27246810/insights-into-islet-development-and-biology-through-characterization-of-a-human-ipsc-derived-endocrine-pancreas-model
#15
Martijn van de Bunt, Majlinda Lako, Amy Barrett, Anna L Gloyn, Mattias Hansson, Mark I McCarthy, Nicola L Beer, Christian Honoré
Directed differentiation of stem cells offers a scalable solution to the need for human cell models recapitulating islet biology and T2D pathogenesis. We profiled mRNA expression at 6 stages of an induced pluripotent stem cell (iPSC) model of endocrine pancreas development from 2 donors, and characterized the distinct transcriptomic profiles associated with each stage. Established regulators of endodermal lineage commitment, such as SOX17 (log2 fold change [FC] compared to iPSCs = 14.2, p-value = 4.9 × 10(-5)) and the pancreatic agenesis gene GATA6 (log2 FC = 12...
April 18, 2016: Islets
https://www.readbyqxmd.com/read/27238020/sensory-neurons-that-detect-stretch-and-nutrients-in-the-digestive-system
#16
Erika K Williams, Rui B Chang, David E Strochlic, Benjamin D Umans, Bradford B Lowell, Stephen D Liberles
Neural inputs from internal organs are essential for normal autonomic function. The vagus nerve is a key body-brain connection that monitors the digestive, cardiovascular, and respiratory systems. Within the gastrointestinal tract, vagal sensory neurons detect gut hormones and organ distension. Here, we investigate the molecular diversity of vagal sensory neurons and their roles in sensing gastrointestinal inputs. Genetic approaches allowed targeted investigation of gut-to-brain afferents involved in homeostatic responses to ingested nutrients (GPR65 neurons) and mechanical distension of the stomach and intestine (GLP1R neurons)...
June 30, 2016: Cell
https://www.readbyqxmd.com/read/27160388/a-missense-variant-in-glp1r-gene-is-associated-with-the-glycaemic-response-to-treatment-with-gliptins
#17
LETTER
M Javorský, I Gotthardová, L Klimčáková, M Kvapil, J Židzik, Z Schroner, P Doubravová, I Gala, I Dravecká, I Tkáč
Gliptins act by increasing endogenous incretin levels. Glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic peptide receptor (GIPR) are their indirect drug targets. Variants of GLP1R and GIPR have previously been associated with the incretin effect. The aim of the present pilot study was to examine associations of the GLP1R and GIPR gene variants with the glycaemic response to gliptins. A total of 140 consecutive patients with type 2 diabetes were followed-up 6 months after initiation of gliptin treatment...
September 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27068334/glucoregulatory-endocrine-and-morphological-effects-of-p5k-hymenochirin-1b-in-mice-with-diet-induced-glucose-intolerance-and-insulin-resistance
#18
Bosede O Owolabi, Opeolu O Ojo, Dinesh K Srinivasan, J Michael Conlon, Peter R Flatt, Yasser H A Abdel-Wahab
The frog skin host-defence peptide hymenochirin-1B has been shown to stimulate insulin release in vitro from isolated pancreatic islets and BRIN-BD11 clonal β-cells. This study examines the effects of 28-day administration of a more potent analogue [P5K]hymenochirin-1B ([P5K]hym-1B) (75 nmol·kg(-1) body weight) to high-fat-fed mice with obesity, glucose intolerance and insulin resistance. Treatment with [P5K]hym-1B significantly decreased plasma glucose concentrations and improved glucose tolerance, insulin secretion, insulin sensitivity and increased the magnitude of the incretin effect (difference in response to oral vs intraperitoneal glucose loads)...
July 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27045241/-the-state-of-the-art-of-imaging-in-gastroenteropancreatic-neuroendocrine-tumors
#19
REVIEW
Xiaochen Yao, Feng Wang
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are neoplasms presenting unpredictable and unusual biologic behavior that causes many clinical challenges. NETs can produce a variety of metabolically active substances (hormones and amines) leading to distinct clinical syndromes. This review will discuss the imaging techniques for the diagnosis of GEP-NETs including ultrasonography, CT, MRI and ultrasound endoscope. In this article, Gallium-68 labeled peptide binding to G protein coupled receptor including SSTR, CCKR1 and GLP1R is addressed, and the application of Gallium-68 labeled somatostin analogues and PET-CT for diagnosis of GEP-NETs is evaluated...
January 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/27035653/long-term-exposure-of-pancreatic-%C3%AE-cells-to-palmitate-results-in-srebp-1c-dependent-decreases-in-glp-1-receptor-signaling-via-creb-and-akt-and-insulin-secretory-response
#20
Annalisa Natalicchio, Giuseppina Biondi, Nicola Marrano, Rossella Labarbuta, Federica Tortosa, Rosaria Spagnuolo, Rossella D'Oria, Emanuele Carchia, Anna Leonardini, Angelo Cignarelli, Sebastio Perrini, Luigi Laviola, Francesco Giorgino
The effects of prolonged exposure of pancreatic β-cells to high saturated fatty acids on glucagon-like peptide-1 (GLP-1) action were investigated. Murine islets, human pancreatic 1.1B4 cells, and rat INS-1E cells were exposed to palmitate for 24 hours. mRNA and protein expression/phosphorylation were measured by real-time RT-PCR and immunoblotting, respectively. Specific short interfering RNAs were used to knockdown expression of the GLP-1 receptor (Glp1r) and Srebf1. Insulin release was assessed with a specific ELISA...
June 2016: Endocrinology
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