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Glp 1 agonist

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https://www.readbyqxmd.com/read/28920919/age-dependent-human-%C3%AE-cell-proliferation-induced-by-glucagon-like-peptide-1-and-calcineurin-signaling
#1
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...
September 18, 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
#2
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
#3
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-1could directly impact osteoblast-mediated bone forming 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 14, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28919062/progress-and-challenges-in-anti-obesity-pharmacotherapy
#4
REVIEW
Daniel H Bessesen, Luc F Van Gaal
Obesity is a serious and growing worldwide health challenge. Healthy lifestyle choices are the foundation of obesity treatment. However, weight loss can lead to physiological adaptations that promote weight regain. As a result, lifestyle treatment alone typically produces only modest weight loss that is difficult to sustain. In other metabolic diseases, pharmacotherapy is an accepted adjunct to lifestyle. Several anti-obesity drugs have been approved in the USA, European Union, Australia, and Japan including sympathomimetics, pancreatic lipase inhibitors, GABAA receptor activators, a serotonin 2C receptor agonist, opioid antagonist, dopamine-norepinephrine reuptake inhibitor, and glucagon-like peptide-1 (GLP-1) receptor agonists...
September 14, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28918389/glucagon-like-peptide-1-receptor-agonists-for-the-management-of-obesity-and-non-alcoholic-fatty-liver-disease-a-novel-therapeutic-option
#5
REVIEW
Gauri Dhir, Kenneth Cusi
Obesity is a major risk factor for the development of type 2 diabetes mellitus (T2DM), and is associated with a cluster of metabolic factors that lead to poor cardiovascular outcomes. In non-alcoholic fatty liver disease (NAFLD), liver fat (triglyceride) accumulation closely mirrors adipose tissue dysfunction and insulin resistance in obesity and T2DM. It is now recognized as the most common chronic liver disease in Westernized societies, often progressing to more severe forms of the disease such as nonalcoholic steatohepatitis (NASH), or cirrhosis and hepatocellular carcinoma...
September 15, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28914987/diabetes-news
#6
Ann M Carracher, Payal H Marathe, Kelly L Close
More than 31,000 attendeesfrom around the world gathered in Barcelona, Spain for the 2017 European Society of Cardiology conference. In presentinga post-hoc analysis of the Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes(LEADER)(1) trial, Dr Neil Poulter (Imperial College London, UK) showedthat results are still positive, indicating cardioprotection, after adjusting for baseline history of stroke or myocardial infarction (MI), which had no mediating effect on the significant association between Novo Nordisk's (Copenhagen, Denmark) glucagon-like peptide-1 (GLP-1) agonist Victoza (liraglutide) and cardiovascular risk reduction...
September 15, 2017: Journal of Diabetes
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
#7
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/28911306/management-of-blood-pressure-and-heart-rate-in-patients-with-diabetes-mellitus
#8
Ioanna Gouni-Berthold, Ruth Hanssen, Lisa Ravarani, Heiner K Berthold
BACKGROUND: In patients with diabetes mellitus (DM) there is a clear association between blood pressure (BP) levels and macrovascular and microvascular complications. However, the BP targets that need to be achieved for optimal outcomes remain controversial. METHODS: The purpose of this narrative review is to discuss BP targets and management in patients with DM. The subject of elevated heart rate, which has been associated with mortality in many populations, and which is observed in some patients with DM will also be addressed...
June 8, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28895639/the-pi3k-akt1-foxo1-translocation-pathway-mediates-exf-effects-on-nit-1-cell-survival
#9
Guo-Jiang Hou, Cai-Na Li, Yi Huan, Shuai-Nan Liu, Quan Liu, Min-Zhi Liu, Zhu-Fang Shen
EXf, a glucagon-like peptide 1 (GLP-1) receptor agonist, stimulates β-cell proliferation and reduces apoptosis in diabetic animal models, but the underlying mechanisms are not fully understood. We constructed a FoxO1-GFP fusion protein expression plasmid and transiently transfected it into NIT-1 cells to investigate whether FoxO1 mediates EXf effects on NIT-1 cell survival. Our results showed that EXf could increase cell viability by inhibiting apoptosis and stimulating proliferation, and it could also promote the translocation of the FoxO1-GFP fusion protein from the nucleus to the cytoplasm in NIT-1 cells...
September 11, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28895030/type-2-diabetes-and-cardiovascular-prevention-the-dogmas-disputed
#10
Dario Giugliano, Maria Ida Maiorino, Giuseppe Bellastella, Katherine Esposito
In randomized controlled trials (RCTs), more intensive glucose control in patients with type 2 diabetes leads to a modest (9%) reduction in major cardiovascular events (MACE), associated with a 20% reduction of kidney events and 13% reduction of eye events. The FDA issued guidance in 2008 led to the conduct of numerous cardiovascular outcomes (CVOT) trials to assess cardiovascular safety of new antihyperglycemic therapies in patients with type 2 diabetes. The results of these trials show that insulin glargine, three different dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin, alogliptin, and sitagliptin) and lixisenatide (a glucagon like peptide-1 receptor agonist) produce no significant difference in CVOT when compared with usual care or placebo...
September 11, 2017: Endocrine
https://www.readbyqxmd.com/read/28894748/new-antihyperglycemic-drugs-and-heart-failure-synopsis-of-basic-and-clinical-data
#11
REVIEW
Dirk von Lewinski, Ewald Kolesnik, Markus Wallner, Michael Resl, Harald Sourij
The assessment of the cardiovascular safety profile of any newly developed antihyperglycemic drug is mandatory before registration, as a meta-analysis raised alarm describing a significant increase in myocardial infarction with the thiazolidinedione rosiglitazone. The first results from completed cardiovascular outcome trials are already available: TECOS, SAVOR-TIMI, and EXAMINE investigated dipeptidyl peptidase 4 (DPP-4) inhibitors, ELIXA, LEADER, and SUSTAIN-6 investigated glucagon-like peptide 1 (GLP-1) receptor agonists, and EMPA-REG OUTCOME and CANVAS investigated sodium-dependent glucose transporter 2 (SGLT-2) inhibitors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28879786/pharmacological-management-of-type-2-diabetes-what-s-new-in-2017
#12
André J Scheen
Introduction Novelties in the management of type 2 diabetes are dominated by the commercialisation of new glucose-lowering agents, which offer alternatives to older antidiabetic medications, and by the publication of several prospective placebo-controlled outcome trials, which demonstrated not only cardiovascular safety but also cardiovascular and renal protection with some new medications. Areas covered Updates regarding the use of glucose-lowering agents are discussed from a clinical point of view. Some new viewpoints concern older antidiabetic agents such as metformin, sulfonylureas and glitazones whose benefit-risk balance has been revisited, especially in high risk patients...
September 7, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28875722/diabetes-injectable-therapy-type-2-diabetes-management-in-danish-practice
#13
Daniel Sterzi, Sébastien Auziere, Marie Markert Jensen, Sandra Lopes
Most diabetes care is done by GPs in Denmark. This study aimed to identify the barriers for GPs to initiate injectable therapies and reasons for referral to specialists. The web-interview conducted included 85 GPs, and 30 specialists experienced in type 2 diabetes (T2D). GPs felt more comfortable with initiating the 1(st) injectable therapy (defined as a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or basal insulin) than the 2(nd) (defined as adding a basal insulin in patients treated with a GLP-1 RA (± OADs), or adding either a GLP-1 RA or a bolus insulin in patients treated with basal insulin (± OADs)...
September 6, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28873389/treatment-of-diabetes-and-obesity-by-rationally-designed-peptide-agonists-functioning-at-multiple-metabolic-receptors
#14
Noushafarin Khajavi, Heike Biebermann, Matthias Tschöp, Richard DiMarchi
Obesity and its comorbidities such as type 2 diabetes constitute major worldwide health threats, and the identification of an effective medical intervention has emerged as a global priority. The limited effectiveness of historical, anti-obesity treatments is commonly attributed to the complexity of the disease and the redundancy of metabolic regulatory mechanisms that sustain body weight. At the forefront of obesity research is the development of combinational drug therapies that simultaneously target multiple regulatory pathways, which promote dysfunctional metabolism...
2017: Endocrine Development
https://www.readbyqxmd.com/read/28873383/incretins-and-their-endocrine-and-metabolic-functions
#15
Jochen Seufert
Incretins are hormones secreted into the blood stream from the gut mucosa in response to nutrient intake. They have been characterized based on their capacity to lower blood glucose levels. The more potent reduction of blood glucose coupled to a more intensive stimulation of insulin secretion, in response to oral glucose uptake, as compared to intravenous glucose infusion has further been termed the "incretin effect." As a prototype incretin hormone, the biology of glucagon-like peptide 1 (GLP-1) has been intensively studied...
2017: Endocrine Development
https://www.readbyqxmd.com/read/28871349/recent-insights-into-pharmacologic-cardiovascular-risk-reduction-in-type-2-diabetes-mellitus
#16
Scott L Purga, Mandeep Sidhu, Michael Farkouh, Joshua Schulman-Marcus
Diabetes mellitus (DM) affects nearly 30 million Americans and carries an increased risk of macrovascular complications of myocardial infarction, stroke, and cardiovascular death. While aggressive cardiovascular risk factor reduction has long been advocated in patients with diabetes, clinical trials have only recently demonstrated that such reductions result in improved outcomes. This review discusses recent evidence for risk reduction strategies and therapies with a focus on the management of glycemia, dyslipidemia, and hypertension...
September 4, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28870630/glp-1-receptor-agonists-an-example-of-the-challenge-for-animal-models-to-predict-plaque-instability-rupture-and-cardiovascular-outcomes
#17
EDITORIAL
Ya-Lan Ying, Yung-Chih Chen, Karin Jandeleit-Dahm, Karlheinz Peter
No abstract text is available yet for this article.
August 18, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28870145/real-world-use-and-modeled-impact-of-glucose-lowering-therapies-evaluated-in-recent-cardiovascular-outcomes-trials-an-ncdr%C3%A2-research-to-practice-project
#18
Suzanne V Arnold, Silvio E Inzucchi, Fengming Tang, Darren K McGuire, Sanjeev N Mehta, Thomas M Maddox, Abhinav Goyal, Laurence S Sperling, Daniel Einhorn, Nathan D Wong, Kamlesh Khunti, Carolyn Sp Lam, Mikhail Kosiborod
Aims Recent trials (EMPA-REG OUTCOME and Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER]) have shown improved cardiovascular (CV) mortality with specific currently available glucose-lowering medications (empagliflozin and liraglutide, respectively), but were limited to selected patient populations. We sought to evaluate the current use and potential real-world impact of empagliflozin (and other sodium-glucose co-transporter 2 inhibitors [SGLT2is]) and liraglutide (and other glucagonlike peptide-1 receptor agonist [GLP-1 RAs]) among patients in the Diabetes Collaborative Registry (DCR)...
January 1, 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28869249/glp-1-and-the-kidney-from-physiology-to-pharmacology-and-outcomes-in-diabetes
#19
REVIEW
Marcel H A Muskiet, Lennart Tonneijck, Mark M Smits, Michaël J B van Baar, Mark H H Kramer, Ewout J Hoorn, Jaap A Joles, Daniël H van Raalte
The gastrointestinal tract - the largest endocrine network in human physiology - orchestrates signals from the external environment to maintain neural and hormonal control of homeostasis. Advances in understanding entero-endocrine cell biology in health and disease have important translational relevance. The gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) is secreted upon meal ingestion and controls glucose metabolism by modulating pancreatic islet cell function, food intake and gastrointestinal motility, amongst other effects...
September 4, 2017: Nature Reviews. Nephrology
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
#20
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
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