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https://www.readbyqxmd.com/read/28538729/cryo-em-structure-of-the-activated-glp-1-receptor-in-complex-with-a-g-protein
#1
Yan Zhang, Bingfa Sun, Dan Feng, Hongli Hu, Matthew Chu, Qianhui Qu, Jeffrey T Tarrasch, Shane Li, Tong Sun Kobilka, Brian K Kobilka, Georgios Skiniotis
Glucagon-like peptide 1 (GLP-1) is a hormone with essential roles in regulating insulin secretion, carbohydrate metabolism and appetite. GLP-1 effects are mediated through binding to the GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor (GPCR) that signals primarily through the stimulatory G protein Gs. Class B GPCRs are important therapeutic targets; however, our understanding of their mechanism of action is limited by the lack of structural information on activated and full-length receptors. Here we report the cryo-electron microscopy structure of the peptide-activated GLP-1R-Gs complex at near atomic resolution...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28534519/two-forms-of-death-in-ageing-caenorhabditis-elegans
#2
Yuan Zhao, Ann F Gilliat, Matthias Ziehm, Mark Turmaine, Hongyuan Wang, Marina Ezcurra, Chenhao Yang, George Phillips, David McBay, William B Zhang, Linda Partridge, Zachary Pincus, David Gems
Ageing generates senescent pathologies, some of which cause death. Interventions that delay or prevent lethal pathologies will extend lifespan. Here we identify life-limiting pathologies in Caenorhabditis elegans with a necropsy analysis of worms that have died of old age. Our results imply the presence of multiple causes of death. Specifically, we identify two classes of corpse: early deaths with a swollen pharynx (which we call 'P deaths'), and later deaths with an atrophied pharynx (termed 'p deaths'). The effects of interventions on lifespan can be broken down into changes in the frequency and/or timing of either form of death...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28533434/lysophosphatidylinositol-induced-activation-of-the-cation-channel-trpv2-triggers-glucagon-like-peptide-1-secretion-in-enteroendocrine-l-cells
#3
Kazuki Harada, Tetsuya Kitaguchi, Taichi Kamiya, Kyaw Htet Aung, Kazuaki Nakamura, Kunihiro Ohta, Takashi Tsuboi
The lysophosphatidylinositol (LPI) has crucial roles in multiple physiological processes, including insulin exocytosis from pancreatic islets. However, the role of LPI in secretion of glucagon like peptide-1 (GLP-1), a hormone that enhances glucose-induced insulin secretion, is unclear. Here, we used the murine enteroendocrine L cell line GLUTag and primary murine small intestinal cells to elucidate the mechanism of LPI-induced GLP-1 secretion. Exogenous LPI addition increased intracellular Ca2+ concentrations ([Ca2+]i) in GLUTag cells and induced GLP-1 secretion from both GLUTag and acutely prepared primary intestinal cells...
May 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28533296/glp-1r-as-a-target-for-the-treatment-of-diabetic-retinopathy-friend-or-foe
#4
Rafael Simó, Cristina Hernández
Glucagon-like peptide 1 receptor (GLP-1R) agonists are increasingly being used as treatment for type 2 diabetes. Since the U.S. Food and Drug Administration published recommendations about the cardiovascular safety of new antidiabetes therapies for treating type 2 diabetes in 2008, the results of two outstanding clinical trials using GLP-1R agonists addressing this issue (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation [LEADER] and Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6]) have been published...
June 2017: Diabetes
https://www.readbyqxmd.com/read/28533020/the-role-of-pyy-in-pancreatic-islet-physiology-and-surgical-control-of-diabetes
#5
REVIEW
Claudia Guida, Sam Stephen, Romain Guitton, Reshma D Ramracheya
Bariatric surgery in obese individuals leads to rapid and lasting remission of type 2 diabetes (T2D). This phenomenon occurs independently of weight loss possibly via a combination of factors. The incretin hormone GLP-1 has so far been recognised as a critical factor. However, recent data have indicated that elevation in another gut hormone, peptide tyrosine tyrosine (PYY), may drive the beneficial effects of surgery. Here we discuss recent findings on PYY-mediated control of glucose homeostasis and its role in diabetes, in the context of what is known for GLP-1...
May 19, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28531784/gut-microbiota-mediated-benefits-of-barley-kernel-products-on-metabolism-gut-hormones-and-inflammatory-markers-as-affected-by-co-ingestion-of-commercially-available-probiotics-a-randomized-controlled-study-in-healthy-subjects
#6
Anne Nilsson, Elin Johansson-Boll, Jonna Sandberg, Inger Björck
BACKGROUND AND AIMS: Barley kernel based products have been shown to induce benefits on blood glucose regulation, cardio-metabolic risk markers and appetite regulating hormones in a time perspective of 11-16 h after intake. The mechanisms have been assigned to gut fermentation of indigestible carbohydrates. The purpose of the present study was to evaluate if the modulatory effects of barley on markers of metabolic- and appetite regulation are affected by a dietary background including a mixture of commercially available probiotics...
October 2016: Clinical Nutrition ESPEN
https://www.readbyqxmd.com/read/28528456/pharmacologic-treatment-of-dyslipidemia-in-diabetes-a-case-for-therapies-in-addition-to-statins
#7
REVIEW
Abeer Anabtawi, Patrick M Moriarty, John M Miles
PURPOSE OF REVIEW: The purpose of the study is to review the use of statins and the role of both non-statin lipid-lowering agents and diabetes-specific medications in the treatment of diabetic dyslipidemia. RECENT FINDINGS: Statins have a primary role in the treatment of dyslipidemia in people with type 2 diabetes, defined as triglyceride levels >200 mg/dl and HDL cholesterol levels <40 mg/dL. A number of clinical trials suggest that treatment with a fibrate may reduce cardiovascular events...
July 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28526921/glp-1-signalling-compensates-for-impaired-insulin-signalling-in-regulating-beta-cell-proliferation-in-%C3%AE-irko-mice
#8
Dan Kawamori, Jun Shirakawa, Chong Wee Liew, Jiang Hu, Tomoaki Morioka, Alokesh Duttaroy, Bryan Burkey, Rohit N Kulkarni
AIMS/HYPOTHESIS: We aimed to investigate potential interactions between insulin and glucagon-like peptide (GLP)-1 signalling pathways in the regulation of beta cell-cycle dynamics in vivo, in the context of the therapeutic potential of GLP-1 to modulate impaired beta cell function. METHODS: Beta cell-specific insulin receptor knockout (βIRKO) mice, which exhibit beta cell dysfunction and an age-dependent decrease in beta cell mass, were treated with the dipeptidyl peptidase-4 inhibitor vildagliptin...
May 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28526416/treatment-strategy-for-type-2-diabetes-with-obesity-focus-on-glucagon-like-peptide-1-receptor-agonists
#9
REVIEW
Qiuhe Ji
PURPOSE: The progressive nature of type 2 diabetes mellitus (T2DM) calls for step-wise intensification of therapy for maintaining normal glycemic levels and lowering cardiovascular (CV) risk. Because obesity is a prominent risk factor and comorbidity of T2DM, it further elevates the CV risk in T2DM. Therefore, it is vital to manage weight, obesity, and glycemic parameters for effective T2DM management. Few oral antidiabetic drugs (sulfonylureas and thiazolidinediones) and insulin are not suitable for obese patients with T2DM because these drugs cause weight gain...
May 16, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28526379/the-polish-intestinal-failure-centres-consensus-on-the-use-of-teduglutide-for-the-treatment-of-short-bowel-syndrome
#10
Stanisław Klek, Marek Kunecki, Jacek Sobocki, Konrad Matysiak, Katarzyna Karwowska, Krystyna Urbanowicz
OBJECTIVE: Teduglutide is an active, glucagon-like peptide (GLP)-2 analog with proven clinical efficacy regarding intestinal adaptation in patients with short bowel syndrome (SBS). There are two factors that preclude its reimbursement, and thereby, its availability: its cost (reaching ∼$300,000/y)-which significantly exceeds the cost of home parenteral nutrition (HPN) in most countries-and the lack of clear guidelines. The aim of this study was to create evidence-based working criteria for the use of teduglutide that could be used in clinical settings...
June 2017: Nutrition
https://www.readbyqxmd.com/read/28523587/erratum-to-glucagon-like-peptide-1-receptor-agonists-glp-1ras-in-the-brain-adipocyte-axis
#11
Bruno Geloneze, José Carlos de Lima-Júnior, Lício A Velloso
No abstract text is available yet for this article.
May 18, 2017: Drugs
https://www.readbyqxmd.com/read/28523577/ffa3-activation-stimulates-duodenal-bicarbonate-secretion-and-prevents-nsaid-induced-enteropathy-via-the-glp-2-pathway-in-rats
#12
Hyder Said, Yasutada Akiba, Kazuyuki Narimatsu, Koji Maruta, Ayaka Kuri, Ken-Ichi Iwamoto, Atsukazu Kuwahara, Jonathan D Kaunitz
BACKGROUND: Therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enteropathy in humans and experimental animals, a cause of considerable morbidity. Unlike foregut NSAID-associated mucosal lesions, most treatments for this condition are of little efficacy. We propose that the endogenously released intestinotrophic hormone glucagon-like peptide-2 (GLP-2) prevents the development of NSAID-induced enteropathy. Since the short-chain fatty acid receptor FFA3 is expressed on enteroendocrine L cells and on enteric nerves in the gastrointestinal tract, we further hypothesized that activation of FFA3 on L cells protects the mucosa from injury via GLP-2 release with enhanced duodenal HCO3(-) secretion...
May 18, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28523483/modeling-the-long-term-cost-effectiveness-of-ideglira-in-patients-with-type-2-diabetes-who-are-failing-to-meet-glycemic-targets-on-basal-insulin-alone-in-the-netherlands
#13
Barnaby Hunt, Divina Glah, Maarten van der Vliet
INTRODUCTION: Insulin degludec/liraglutide (IDegLira) is the first basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1 RA) in a single pen injection device, and a once-daily treatment option for patients with type 2 diabetes mellitus (T2DM) who are uncontrolled on basal insulin and require treatment intensification. The objective of this analysis was to evaluate the long-term cost-effectiveness of IDegLira versus basal-bolus therapy (insulin glargine U100 + 3× daily insulin aspart) for patients with T2DM uncontrolled on basal insulin [HbA1c >53 mmol/mol (>7%)] in the Netherlands...
May 18, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28523422/usefulness-of-the-non-conventional-caenorhabditis-elegans-model-to-assess-candida-virulence
#14
Marcelo Ortega-Riveros, Iker De-la-Pinta, Cristina Marcos-Arias, Guillermo Ezpeleta, Guillermo Quindós, Elena Eraso
Invasive candidiasis is caused mainly by Candida albicans, but other Candida species have increasing etiologies. These species show different virulence and susceptibility levels to antifungal drugs. The aims of this study were to evaluate the usefulness of the non-conventional model Caenorhabditis elegans to assess the in vivo virulence of seven different Candida species and to compare the virulence in vivo with the in vitro production of proteinases and phospholipases, hemolytic activity and biofilm development capacity...
May 18, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28522587/preclinical-evaluation-of-medi0641-a-pyrrolobenzodiazepine-conjugated-antibody-drug-conjugate-targeting-5t4
#15
Jay Harper, Christopher Lloyd, Nazzareno Dimasi, Dorin Toader, Rose Marwood, Leeanne Lewis, David Bannister, Jelena Jovanovic, Ryan Fleming, Francois d'Hooge, Shenlan Mao, Allison M Marrero, Martin Korade, Patrick Strout, Linda Xu, Cui Chen, Leslie Wetzel, Shannon Breen, Lilian van Vlerken-Ysla, Sanjoo Jalla, Marlon Rebelatto, Helen Zhong, Elaine M Hurt, Mary Jane Hinrichs, Keven Huang, Philip W Howard, David A Tice, Robert E Hollingsworth, Ronald Herbst, Adeela Kamal
Antibody-drug conjugates (ADCs) are used to selectively deliver cytotoxic agents to tumors and have the potential for increased clinical benefit to cancer patients. 5T4 is an oncofetal antigen overexpressed on the cell surface in many carcinomas on both bulk tumor cells as well as cancer stem cells (CSCs), has very limited normal tissue expression, and can internalize when bound by an antibody. An anti-5T4 antibody was identified and optimized for efficient binding and internalization in a target-specific manner, and engineered cysteines were incorporated into the molecule for site-specific conjugation...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522196/impact-of-glucose-lowering-therapies-on-risk-of-stroke-in-type-2-diabetes
#16
REVIEW
F Bonnet, A J Scheen
Patients with type 2 diabetes (T2D) have an increased risk of stroke compared with people without diabetes. However, the effects of glucose-lowering drugs on risk of ischaemic stroke in T2D have been less extensively investigated than in coronary heart disease. Some evidence, including the UKPDS, has suggested a reduced risk of stroke with metformin, although the number of studies is limited. Inhibition of the KATP channels increases ischaemic brain lesions in animals. This is in agreement with a recent meta-analysis showing an increased risk of stroke with sulphonylureas vs...
May 15, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28522195/a-dpp-iv-resistant-glucagon-like-peptide-2-dimer-with-enhanced-activity-against-radiation-induced-intestinal-injury
#17
Jintao Gu, Shuo Liu, Nan Mu, Tonglie Huang, Wangqian Zhang, Huadong Zhao, Zhen Shu, Cun Zhang, Qiang Hao, Weina Li, Xiaochang Xue, Wei Zhang, Yingqi Zhang
Although radiotherapy is a highly effective treatment for abdominal or pelvic cancer patients, it can increase the incidence of severe gastrointestinal (GI) toxicity. As an intestinal growth factor, glucagon-like peptide 2 (GLP-2) has been shown to improve the preclinical models of both short bowel syndrome and inflammatory bowel disease by stimulating intestinal growth. Teduglutide ([Gly(2)]GLP-2), a recombinant human GLP-2 variant, has a prolonged half-life and stability as compared to the native GLP-2 peptide, but still requires daily application in the clinic...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28520810/long-chain-saturated-and-unsaturated-fatty-acids-exert-opposing-effects-on-viability-and-function-of-glp-1-producing-cells-mechanisms-of-lipotoxicity
#18
Ketan Thombare, Stelia Ntika, Xuan Wang, Camilla Krizhanovskii
BACKGROUND AND AIM: Fatty acids acutely stimulate GLP-1 secretion from L-cells in vivo. However, a high fat diet has been shown to reduce the density of L-cells in the mouse intestine and a positive correlation has been indicated between L-cell number and GLP-1 secretion. Thus, the mechanism of fatty acid-stimulated GLP-1 secretion, potential effects of long-term exposure to elevated levels of different fatty acid species, and underlying mechanisms are not fully understood. In the present study, we sought to determine how long-term exposure to saturated (16:0) and unsaturated (18:1) fatty acids, by direct effects on GLP-1-producing cells, alter function and viability, and the underlying mechanisms...
2017: PloS One
https://www.readbyqxmd.com/read/28515711/the-impact-of-glucagon-like-peptide-1-on-bone-metabolism-and-its-possible-mechanisms
#19
REVIEW
Chenhe Zhao, Jing Liang, Yinqiu Yang, Mingxiang Yu, Xinhua Qu
The impact of antidiabetic drugs on bone metabolism is drawing increasing attention due to the discovery of a correlation between type 2 diabetes mellitus (T2DM) and osteoporosis. Glucagon-like peptide-1 (GLP-1) receptor agonists are a novel and promising class of drugs for T2DM, which may also have clinical applications in bone tissue disorders. This review examines the impact of GLP-1 on bone metabolism, including enhancement of bone mineral density and improvement of bone quality. However, the precise effect of GLP-1 on fracture risk has not been unambiguously defined...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28515501/ismp-medication-error-report-analysis-potential-issues-with-new-basal-insulin-glp-1-fixed-combinations-hydroxyzine-hydroxyurea-mix-up-concomitant-use-of-entresto-and-ace-inhibitors-can-lead-to-serious-outcomes-more-outpatient-oral-cancer-drugs-should-be-in
#20
Michael R Cohen, Judy L Smetzer
These medication errors have occurred in health care facilities at least once. They will happen again-perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program...
April 2017: Hospital Pharmacy
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