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GLP-1 Analogues

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https://www.readbyqxmd.com/read/28433618/evidence-based-recommendations-for-insulin-intensification-strategies-after-basal-insulin-in-type-2-diabetes
#1
Sujoy Ghosh, A G Unnikrishnan, Banshi Saboo, Jothydev Kesavadev, S R Aravind, Sarita Bajaj, Rajesh Rajput, Krishna Seshadri, Narsingh Verma, Arvind Gupta, Brij Mohan Makkar, Mihir Saikia, Shailaja Kale, Suresh Damodaran, Ashish Dengra, T K M Eashwar, Anuj Maheshwari, Sharad Pendsey, Sanjeev R Phatak, Surendra Kumar Sharma, Surya Kumar Singh, A Ramachandran, Abdul H Zargar, Shashank R Joshi, Shaukat M Sadikot
Over the time due to progressive nature of diabetes, proactive intensification of the existing insulin therapy becomes imminent as it minimizes patients' exposure to chronic hypo/hyperglycaemia and reduces weight gain while achieving individualized glycaemic targets. This review focuses on the strength of evidence behind various options for intensification, primarily the insulins as also the GLP-1 analogues. The recommendations presented here are meant to serve as a guide for the physician managing type 2 diabetes patients requiring insulin intensification upon failing of basal insulin therapy...
April 5, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28413488/the-effects-of-glp-1-analogues-on-pre-diabetes-of-the-children
#2
Qing-Xia Zhou, Zi-Yu Wang, Hua-Feng Zhao, Shan Wang
The aim of the study was to evaluate the clinical efficacy of glucagon-like peptide-1 (GLP-1) analogues in children of pre-diabetes to delay or reverse the development of pre-diabetes into the state of diabetes by early intervention. Prospective and randomized controlled clinical trials were performed in 42 cases of newly diagnosed pre-diabetes in children. The sample size was randomly divided into the two groups. The first group included 21 subjects comprising the lifestyle intervention group, i.e., control group, and the second group included 21 subjects comprising the lifestyle intervention+GLP-1 analogues liraglutide group, i...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28408435/neurturin-and-a-glp-1-analogue-act-synergistically-to-alleviate-diabetes-in-zucker-diabetic-fatty-rats
#3
James L Trevaskis, Chester Bittencourt Sacramento, Hani Jouihan, Safina Ali, John Le Lay, Stephanie Oldham, Nicholas Bhagroo, Brandon B Boland, Jennifer Cann, Yuan Chang, Terrence O'Day, Victor Howard, Christina Reers, Maria Sorhede Winzell, David M Smith, Michael Feigh, Pernille Barkholt, Kay Schreiter, Matthias Austen, Uwe Andag, Simon Thompson, Lutz Jermutus, Matthew P Coghlan, Joseph Grimsby, Cord Dohrmann, Christopher J Rhodes, Cristina M Rondinone, Arun Sharma
Neurturin (NRTN), a member of the glial-derived neurotrophic factor (GDNF) family, was identified from an embryonic chicken pancreatic cDNA library in a screen for secreted factors. Here, we assessed the potential antidiabetic activities of NRTN relative to liraglutide, a GLP-1 receptor agonist, in Zucker diabetic fatty (ZDF) rats. Subcutaneous administration of NRTN to 8-week-old male ZDF rats prevented the development of hyperglycemia and improved metabolic parameters similar to liraglutide. NRTN treatment increased pancreatic insulin content and β-cell mass, and prevented deterioration of islet organization...
April 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28405672/glucagon-like-peptide-1-related-peptides-increase-nitric-oxide-effects-to-reduce-platelet-activation
#4
Cristina Barale, Simona Buracco, Franco Cavalot, Chiara Frascaroli, Angelo Guerrasio, Isabella Russo
Glucagon-like peptide 1 (GLP-1) is object of intensive investigation for not only its metabolic effects but also the protective vascular actions. Since platelets exert a primary role in the pathogenesis of atherosclerosis, inflammation and vascular complications, we investigated whether GLP-1 directly influences platelet reactivity. For this purpose, in platelets from 72 healthy volunteers we evaluated GLP-1 receptor (GLP-1R) expression and the effects of a 15-minute incubation with the native form GLP-1(7-36), the N-terminally truncated form GLP-1(9-36) and the GLP-1 analogue Liraglutide (100 nmol/l) on: i) aggregation induced by collagen or arachidonic acid (AA); ii) platelet function under shear stress; iii) cGMP and cAMP synthesis and cGMP-dependent protein kinase (PKG)-induced Vasodilator-Stimulated-Phosphoprotein (VASP) phosphorylation; iv) activation of the signalling molecules Phosphatidylinositol 3-Kinase (PI3-K)/Akt and Mitogen Activated Protein Kinase (MAPK)/ERK-1/2; and v) oxidative stress...
April 13, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28400403/molecular-imaging-in-the-investigation-of-hypoglycaemic-syndromes-and-their-management
#5
David A Pattison, Rodney J Hicks
There has been recent progress in molecular imaging using a variety of cellular targets for the investigation of adult non-diabetic hypoglycaemic syndromes and its integration into patient management. These targets include peptide receptors - somatostatin receptors (SSTR) and glucagon-like peptide-1 receptor (GLP-1R) - the Amine Precursor Uptake and Decarboxylation system utilising the diphydroxyphenylaline (DOPA) analogue 6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine (18F-FDOPA), and glycolytic metabolism with 2-[18F]Fluoro-2-Deoxy-D-Glucose (FDG)...
April 11, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28392407/actions-of-pgla-am1-and-its-a14k-and-a20k-analogues-and-their-therapeutic-potential-as-anti-diabetic-agents
#6
Bosede O Owolabi, Vishal Musale, Opeolu O Ojo, R Charlotte Moffett, Mary K McGahon, Tim M Curtis, J Michael Conlon, Peter R Flatt, Yasser H A Abdel-Wahab
PGLa-AM1 (GMASKAGSVL(10)GKVAKVALKA(20)AL.NH2) was first identified in skin secretions of the frog Xenopus amieti (Pipidae) on the basis of its antimicrobial properties. PGLa-AM1 and its [A14K] and [A20K] analogues produced a concentration-dependent stimulation of insulin release from BRIN-BD11 rat clonal β-cells without cytotoxicity at concentrations up to 3 μM. In contrast, the [A3K] was cytotoxic at concentrations ≥ 30 nM. The potency and maximum rate of insulin release produced by the [A14K] and [A20K] peptides were significantly greater than produced by PGLa-AM1...
April 6, 2017: Biochimie
https://www.readbyqxmd.com/read/28385659/efficacy-and-safety-of-once-weekly-semaglutide-versus-once-daily-sitagliptin-as-an-add-on-to-metformin-thiazolidinediones-or-both-in-patients-with-type-2-diabetes-sustain-2-a-56-week-double-blind-phase-3a-randomised-trial
#7
Bo Ahrén, Luis Masmiquel, Harish Kumar, Mehmet Sargin, Julie Derving Karsbøl, Sanja Hald Jacobsen, Francis Chow
BACKGROUND: Semaglutide is a novel glucagon-like peptide-1 (GLP-1) analogue, suitable for once-weekly subcutaneous administration, in development for treatment of type 2 diabetes. We assessed the efficacy and safety of semaglutide versus the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled on metformin, thiazolidinediones, or both. METHODS: We did a 56-week, phase 3a, randomised, double-blind, double-dummy, active-controlled, parallel-group, multinational, multicentre trial (SUSTAIN 2) at 128 sites in 18 countries...
May 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28363772/characterization-of-signal-bias-at-the-glp-1-receptor-induced-by-backbone-modification-of-glp-1
#8
Marlies V Hager, Lachlan Clydesdale, Samuel H Gellman, Patrick M Sexton, Denise Wootten
The glucagon-like peptide-1 receptor (GLP-1R) is a cla B G protein-coupled receptor that is a major therapeutic target for the treatment of type 2 diabetes. Activation of this receptor promotes insulin secretion and blood glucose regulation. The GLP-1R can initiate signaling through several intracellular pathways upon activation by GLP-1. GLP-1R ligands that preferentially stimulate subsets among the natural signaling pathways ("biased agonists") could be useful as tools for elucidating the consequences of specific pathways and might engender therapeutic agents with tailored effects...
March 28, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28344112/efficacy-and-safety-of-once-weekly-semaglutide-versus-once-daily-insulin-glargine-as-add-on-to-metformin-with-or-without-sulfonylureas-in-insulin-naive-patients-with-type-2-diabetes-sustain-4-a-randomised-open-label-parallel-group-multicentre-multinational
#9
Vanita R Aroda, Stephen C Bain, Bertrand Cariou, Milivoj Piletič, Ludger Rose, Mads Axelsen, Everton Rowe, J Hans DeVries
BACKGROUND: Several pharmacological treatment options are available for type 2 diabetes; however, many patients do not achieve optimum glycaemic control and therefore new therapies are necessary. We assessed the efficacy and safety of semaglutide, a glucagon-like peptide-1 (GLP-1) analogue in clinical development, compared with insulin glargine in patients with type 2 diabetes who were inadequately controlled with metformin (with or without sulfonylureas). METHODS: We did a randomised, open-label, non-inferiority, parallel-group, multicentre, multinational, phase 3a trial (SUSTAIN 4) at 196 sites in 14 countries...
May 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28323117/absorption-metabolism-and-excretion-of-the-glp-1-analogue-semaglutide-in-humans-and-nonclinical-species
#10
Lene Jensen, Hans Helleberg, Ad Roffel, Jan Jaap van Lier, Inga Bjørnsdottir, Palle Jacob Pedersen, Everton Rowe, Julie Derving Karsbøl, Mette Lund Pedersen
Semaglutide is a human glucagon-like peptide-1 analogue in clinical development for the treatment of type 2 diabetes. The absorption, metabolism and excretion of a single 0.5mg/450μCi [16.7MBq] subcutaneous dose of [(3)H]-radiolabelled semaglutide was investigated in healthy human subjects and compared with data from nonclinical studies. Radioactivity in blood, plasma, urine and faeces was determined in humans, rats and monkeys; radioactivity in expired air was determined in humans and rats. Metabolites in plasma, urine and faeces were quantified following profiling and radiodetection...
March 16, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28315374/glp-1-analogue-cjc-1131-prevents-amyloid-%C3%AE-protein-induced-impirments-of-spatial-memory-and-synaptic-plasticity-in-rats
#11
Sheng-Xiao Zhang, Hong-Yan Cai, Xiao-Wen Ma, Li Yuan, Jun Zhang, Zhao-Jun Wang, Yu-Feng Li, Jin-Shun Qi
Although amyloid β protein (Aβ) has been recognized as one of the main pathological characteristics in the brain of Alzheimer's disease (AD), the effective strategies against Aβ neurotoxicity are still deficient up to now. Glucagon-like peptide 1 (GLP-1), a natural gut hormone, was found to be effective in modulating insulin signaling and neural protection, but short half-life limited its clinical application in AD treatment. CJC-1131, a newly designed GLP-1 analogue with very longer half-life, has shown good effectiveness in the treatment of type 2 diabetes mellitus (T2DM)...
March 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28292761/optimization-of-tolerability-and-efficacy-of-dual-amylin-and-calcitonin-receptor-agonist-kbp-089-through-dose-escalation-and-combination-with-a-glp-1-analogue
#12
Sofie Gydesen, Kim Vietz Andreassen, Sara Toftegaard Hjuler, Lars I Hellgren, Morten Asser Karsdal, Kim Henriksen
Amylin and GLP-1 agonism induce a well-known anorexic effect at dose initiation, which is managed by dose escalation. In this study, we investigated how to optimize tolerability, while maintaining efficacy of KBP-089. Furthermore, we tested the GLP-1 add-on potential of KBP-089 in HFD rats. KBP-089 potently activated both the amylin and calcitonin receptors in vitro, demonstrated a prolonged receptor activation, and potently reduced acute food intake. HFD rats dosed every or every second day obtained equal weight loss at study end, albeit with an uneven reduction in both food intake and bodyweight in rats dosed every second day...
March 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28286674/the-effect-of-exercise-intensity-on-total-pyy-and-glp-1-in-healthy-females-a-pilot-study
#13
Jillian R Hallworth, Jennifer L Copeland, Jon Doan, Tom J Hazell
We compared the acute response of anorexigenic signals (total PYY and GLP-1) in response to submaximal and supramaximal exercise. Nine females completed three sessions: (1) moderate-intensity continuous training (MICT; 30 min; 65%  VO2max); (2) sprint interval training (SIT; 6 × 30 sec "all-out" cycling sprints with 4 min recovery); or (3) control (CTRL; no exercise). PYY and GLP-1 were measured via blood samples drawn before, immediately after, and 90 min after exercise. Perceptions of hunger were rated using a visual analogue scale at all blood sampling time points...
2017: Journal of Nutrition and Metabolism
https://www.readbyqxmd.com/read/28245771/current-drug-targets-in-obesity-pharmacotherapy-a-review
#14
Sangeeta P Bhat, Arun Sharma
Obesity, an impending global pandemic, is not being effectively controlled by current measures such as lifestyle modifications, bariatric surgery or available medications. Its toll on health and economy compels us to look for more effective measures. Fortunately, the advances in biology and molecular technology have been in our favour for delineating new pathways in the pathophysiology of obesity and have led to subsequent development of new drug targets. Development of anti-obesity drugs has often been riddled with problems in the past...
February 27, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28242257/exendin-4-inhibits-structural-remodeling-and-improves-ca-2-homeostasis-in-rats-with-heart-failure-via-the-glp-1-receptor-through-the-enos-cgmp-pkg-pathway
#15
Jingjing Chen, Dandan Wang, Fangai Wang, Shaobo Shi, Yuting Chen, Bo Yang, Yanhong Tang, Congxin Huang
The glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 is a long-acting analog of GLP-1, which stimulates insulin secretion and is clinically used in the treatment of type 2 diabetes. Previous studies have demonstrated that GLP-1 agonists and analogs serve as cardioprotective factors in various conditions. Disturbances in calcium cycling are characteristic of heart failure (HF); therefore, the aim of this study was to investigate the effect of exendin-4 (a GLP-1 mimetic) on the regulation of calcium handling and to identify the underlying mechanisms in an HF rat model after myocardial infarction (MI)...
April 2017: Peptides
https://www.readbyqxmd.com/read/28237265/treating-prediabetes-in-the-obese-are-glp-1-analogues-the-answer
#16
Olivia M Farr, Christos S Mantzoros
No abstract text is available yet for this article.
April 8, 2017: Lancet
https://www.readbyqxmd.com/read/28223210/a-novel-glp-1-gip-dual-receptor-agonist-protects-from-6-ohda-lesion-in-a-rat-model-of-parkinson-s-disease
#17
Jaishree Jalewa, Mohit Kumar Sharma, Simon Gengler, Christian Hölscher
The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. GLP-1 analogues are currently on the market as treatments for type II diabetes. We previously showed that the novel dual agonist (DA-JC1) was effective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
February 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28222742/resistant-starch-lowers-postprandial-glucose-and-leptin-in-overweight-adults-consuming-a-moderate-to-high-fat-diet-a-randomized-controlled-trial
#18
Mindy Patterson Maziarz, Sara Preisendanz, Shanil Juma, Victorine Imrhan, Chandan Prasad, Parakat Vijayagopal
BACKGROUND: High-amylose maize resistant starch type 2 (HAM-RS2) stimulates gut-derived satiety peptides and reduces adiposity in animals. Human studies have not supported these findings despite improvements in glucose homeostasis and insulin sensitivity after HAM-RS2 intake which can lower adiposity-related disease risk. The primary objective of this study was to evaluate the impact of HAM-RS2 consumption on blood glucose homeostasis in overweight, healthy adults. We also examined changes in biomarkers of satiety (glucagon-like peptide-1 [GLP-1], peptide YY [PYY], and leptin) and body composition determined by anthropometrics and dual-energy x-ray absorptiometry, dietary intake, and subjective satiety measured by a visual analogue scale following HAM-RS2 consumption...
February 21, 2017: Nutrition Journal
https://www.readbyqxmd.com/read/28222044/endocrine-system-on-chip-for-a-diabetes-treatment-model
#19
Dao Thi Thuy Nguyen, Danny van Noort, In-Kyung Jeong, Sungsu Park
The endocrine system is a collection of glands producing hormones which, among others, regulates metabolism, growth and development. One important group of endocrine diseases is diabetes, which is caused by a deficiency or diminished effectiveness of endogenous insulin. By using a microfluidic perfused 3D cell-culture chip, we developed an 'endocrine system on chip' to potentially be able to screen drugs for the treatment of diabetes by measuring insulin release over time. Insulin-secreting β-cells are located in the pancreas, while L-cells, located in the small intestines, stimulate insulin secretion...
February 21, 2017: Biofabrication
https://www.readbyqxmd.com/read/28216550/the-acute-effects-of-simple-sugar-ingestion-on-appetite-gut-derived-hormone-response-and-metabolic-markers-in-men
#20
Adora M W Yau, John McLaughlin, William Gilmore, Ronald J Maughan, Gethin H Evans
This pilot study aimed to investigate the effect of simple sugar ingestion, in amounts typical of common ingestion, on appetite and the gut-derived hormone response. Seven healthy men ingested water (W) and equicaloric solutions containing 39.6 g glucose monohydrate (G), 36 g fructose (F), 36 g sucrose (S), and 19.8 g glucose monohydrate + 18 g fructose (C), in a randomised order. Serum concentrations of ghrelin, glucose dependent insulinotropic polypeptide (GIP), glucagon like peptide-1 (GLP-1), insulin, lactate, triglycerides, non-esterified fatty acids (NEFA), and d-3 hydroxybutyrate, were measured for 60 min...
February 14, 2017: Nutrients
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