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https://www.readbyqxmd.com/read/28928089/in-vitro-and-in-vivo-studies-supporting-the-therapeutic-potential-of-zp3022-in-diabetes
#1
Jolanta Skarbaliene, Kristoffer T Rigbolt, Keld Fosgerau, Nils Billestrup
GLP-1-gastrin dual agonist ZP3022 has been shown to increase β-cell mass with a concomitant improvement of glycemic control in diabetic mice and rats. Here we tested the in-vitro effects of ZP3022 on β-cell proliferation, islet apoptosis and glucose-stimulated insulin secretion (GSIS) in rat islets of Langerhans. Moreover, gene expression profiling in whole pancreas from Zucker Diabetic Fatty (ZDF) rats was performed to characterize genes differently regulated by short-term treatment with ZP3022. Treatments with exendin-4, gastrin-17 alone or in combination were included in the studies...
September 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28927992/protective-effects-of-the-glp-1-mimetic-exendin-4-in-parkinson-s-disease
#2
REVIEW
Dilan Athauda, Thomas Foltynie
There is increasing interest in the potential role of glucagon-like peptide-1 (GLP-1) receptor agonists as neuroprotective treatments in neurodegenerative diseases including Parkinson's disease following the publication of the results of the Exenatide-PD trial. Of the current GLP-1 receptor agonists already licensed to treat Type 2 diabetes several including exenatide, liraglutide and lixisenatide are the subject of ongoing clinical trials in PD. The underlying rationale for using drugs licensed and effective for T2DM in PD patients therefore needs to be scrutinized, and the results obtained to date critically reviewed...
September 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28924916/erratum-to-microvascular-effects-of-glucagon-like-peptide-1-receptor-agonists-in-type-2-diabetes-a-meta-analysis-of-randomized-controlled-trials
#3
Ilaria Dicembrini, Besmir Nreu, Alessia Scatena, Francesco Andreozzi, Giorgio Sesti, Edoardo Mannucci, Matteo Monami
In the manuscript, the events of nephropathy and retinopathy recorded for the LEADER trial (Marso et al. 2016) were erroneously imputed; the numbers reported in Table 1 for that trial refer to serious adverse events, and not to total events, as stated in Methods. The correct figures are 268 and 416 cases of nephropathy, and 106 and 92 cases of retinopathy in liraglutide and control arms, respectively. As a consequence, the overall risk (MH-OR [95% CI]) of nephropathy and retinopathy with GLP-1RA (vs all comparators) is 0...
September 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28920919/age-dependent-human-%C3%AE-cell-proliferation-induced-by-glucagon-like-peptide-1-and-calcineurin-signaling
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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