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Diabetes AND glp-1

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https://www.readbyqxmd.com/read/28319060/the-anti-diabetic-drug-exenatide-a-glucagon-like-peptide-1-receptor-agonist-counteracts-hepatocarcinogenesis-through-camp-pka-egfr-stat3-axis
#1
M Zhou, M T S Mok, H Sun, A W Chan, Y Huang, A S L Cheng, G Xu
Epidemiological studies have demonstrated a close association of type 2 diabetes and hepatocellular carcinoma (HCC). Exenatide (Ex-4), a potent diabetes drug targeting glucagon-like peptide-1 receptor (GLP-1R), is protective against non-alcoholic fatty liver disease (NAFLD). However, the Ex-4 function and GLP-1R status have yet been explored in HCC. Herein we investigated the effect of Ex-4 in diethylnitrosamine (DEN)-treated mice consuming control or high-fat high-carbohydrate diet. Administration of Ex-4 significantly improved obesity-induced hyperglycemia and hyperlipidemia and reduced HCC multiplicity in obese DEN-treated mice, in which suppressed proliferation and induced apoptosis were confined to tumor cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28318339/exendin-4-does-not-modify-growth-or-apoptosis-of-human-colon-cancer-cells
#2
He Wenjing, Yu Shuang, Li Weisong, Xiao Haipeng
AIM: Glucagon-like peptide-1 (GLP-1) receptor agonists are a kind of very popular antidiabetes drugs. They promote cell proliferation and survival through activation of signaling pathways in human islet cells involving phosphate idylinositol 3 kinase (PI3K) and extracellular regulated kinases 1 and 2 (ERK1/2), which are frequently activated in human colon cancer cells. Then, it is possible that taking GLP-1 receptor (GLP-1R) agonists persistently would induce proliferation of β cells as well as colon cancer cells...
March 20, 2017: Endocrine Research
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
#3
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 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28315192/discrete-choice-experiment-attribute-selection-using-a-multinational-interview-study-treatment-features-important-to-patients-with-type-2-diabetes-mellitus
#4
Anna Rydén, Stephanie Chen, Emuella Flood, Beverly Romero, Susan Grandy
INTRODUCTION: Methods for discrete choice experiment (DCE) attribute and attribute-level selection have not yet been firmly established and are rarely reported in detail. This paper describes a qualitative study designed to inform the development of a DCE survey designed to examine preferences for glucagon-like peptide-1 receptor agonist (GLP-1RA) treatments among patients with type 2 diabetes mellitus. METHODS: The study involved a literature review, interviews with clinical experts, and interviews with GLP-1RA-experienced (i...
March 17, 2017: Patient
https://www.readbyqxmd.com/read/28300673/semi-microbiological-synthesis-of-an-active-lysinoalanine-bridged-analog-of-glucagon-like-peptide-1
#5
Anneke Kuipers, Louwe de Vries, Marcel P de Vries, Rick Rink, Tjibbe Bosma, Gert N Moll
Some modified glucagon-like-peptide-1 (GLP-1) analogs are highly important for treating type 2 diabetes. Here we investigated whether GLP-1 analogs expressed in Lactococcus lactis could be substrates for modification and export by the nisin dehydratase and transporter enzyme. Subsequently we introduced a lysinoalanine by coupling a formed dehydroalanine with a lysine and investigated the structure and activity of the formed lysinoalanine-bridged GLP-1 analog. Our data show: i) GLP-1 fused to the nisin leader peptide is very well exported via the nisin transporter NisT, ii) production of leader-GLP-1 via NisT is higher than via the SEC system, iii) leader-GLP-1 exported via NisT was more efficiently dehydrated by the nisin dehydratase NisB than when exported via the SEC system, iv) individual serines and threonines in GLP-1 are dehydrated by NisB to a significantly different extent, v) an introduced Ser30 is well dehydrated and can be coupled to Lys34 to form a lysinoalanine-bridged GLP-1 analog, vi) a lysinoalanine(30-34) variant's conformation shifts in the presence of 25% trifluoroethanol towards a higher alpha helix content than observed for wild type GLP-1 under identical condition, vii) a lysinoalanine(30-34) GLP-1 variant has retained significant activity...
March 11, 2017: Peptides
https://www.readbyqxmd.com/read/28298900/the-impact-of-bariatric-surgery-on-type-2-diabetes-mellitus-and-the-management-of-hypoglycemic-events
#6
REVIEW
Mahmoud Attia Mohamed Kassem, Michael Andrew Durda, Nicoleta Stoicea, Omer Cavus, Levent Sahin, Barbara Rogers
Recent studies discussed the benefit of bariatric surgery on obese patients diagnosed with type 2 diabetes mellitus (T2DM). Several factors play an essential role in predicting the impact of bariatric surgery on T2DM, such as ABCD score (age, BMI, C-peptide, and duration of the disease), HbA1c, and fasting blood glucose, incretins [glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP)]. DiaRem score known to include factors such as age, HbA1c, medication, and insulin usage used to predict the remission of T2DM, but it has some limitations...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28295962/improving-glycemic-control-in-type-2-diabetes-stimulate-insulin-secretion-or-provide-beta-cell-rest
#7
REVIEW
Daniël H van Raalte, C Bruce Verchere
Type 2 diabetes (T2D) is characterized by a gradual decline of pancreatic beta cell function that determines the progressive course of the disease. While beta-cell failure is an important contributor to hyperglycemia, chronic hyperglycemia itself is also detrimental for beta-cell function, likely by inducing prolonged secretory stress on the beta cell as well as through direct glucotoxic mechanisms that have not been fully defined. For years, research has been carried out in search of therapies targeting hyperglycemia that preserve long-term beta-cell function in T2D, a quest that is still ongoing...
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28294702/safety-and-efficacy-of-a-glucagon-like-peptide-1-receptor-agonist-added-to-basal-insulin-therapy-versus-basal-insulin-with-or-without-a-rapid-acting-insulin-in-patients-with-type-2-diabetes-results-of-a-meta-analysis
#8
Carol H Wysham, Jay Lin, Louis Kuritzky
OBJECTIVE: To consolidate the evidence from randomized controlled trials evaluating the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as add-on to basal insulin therapy in type 2 diabetes (T2D) patients. RESEARCH DESIGN AND METHODS: We searched the EMBASE® and NCBI PubMed (Medline) databases and relevant congress abstracts for randomized controlled trials evaluating the efficacy and safety of GLP-1 RAs as add-on to basal insulin compared with basal insulin with or without rapid-acting insulin (RAI) through 23 May 2016...
March 15, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28294499/a-placebo-controlled-randomised-trial-of-the-addition-of-once-weekly-glp-1-receptor-agonist-dulaglutide-to-titrated-daily-insulin-glargine-in-patients-with-type-2-diabetes-award-9
#9
Paolo Pozzilli, Paul Norwood, Esteban Jodar, Melanie J Davies, Tibor Ivanyi, Honghua Jiang, Brad Woodward, Zvonko Milicevic
AIMS: Compare the addition of weekly dulaglutide versus the addition of placebo to titrated glargine in patients with type 2 diabetes (T2D) with sub-optimal HbA1c . METHODS: Patients (N = 300) from this Phase 3, double-blind, parallel-arm, placebo-controlled study were randomised to weekly subcutaneous injections of dulaglutide 1.5 mg or placebo with titrated daily glargine (mean ± SD baseline dose: 39 ± 22 U), with or without metformin (≥1,500 mg/day)...
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28291655/the-cardiovascular-safety-trials-of-dpp-4-inhibitors-glp-1-agonists-and-sglt2-inhibitors
#10
REVIEW
Matthew H Secrest, Jacob A Udell, Kristian B Filion
In this paper, we review the results of large, double-blind, placebo-controlled randomized trials mandated by the US Food and Drug Administration to examine the cardiovascular safety of newly-approved antihyperglycemic agents in patients with type 2 diabetes. The cardiovascular effects of dipeptidyl peptidase-4 (DPP-4) inhibitors remain controversial: while these drugs did not reduce or increase the risk of primary, pre-specified composite cardiovascular outcomes, one DPP-4 inhibitor (saxagliptin) increased the risk of hospitalization for heart failure in the overall population; another (alogliptin) demonstrated inconsistent effects on heart failure hospitalization across subgroups of patients, and a third (sitagliptin) demonstrated no effect on heart failure...
January 28, 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28290604/glucagon-like-peptide-1-receptor-agonist-ameliorates-the-insulin-resistance-function-of-islet-%C3%AE-cells-via-the-activation-of-pdx-1-jak-signaling-transduction-in-c57-bl6-mice-with-high-fat-diet-induced-diabetes
#11
Tao Hao, Hongtao Zhang, Sheyu Li, Haoming Tian
Long-term exposure to a high-fat diet (HFD) causes glucotoxicity and lipotoxicity in islet β cells and leads to the development of metabolic dysfunctions. Reductions in pancreatic and duodenal homeobox-1 (PDX-1) expression have been shown to induce type 2 diabetes mellitus by causing impairments to islet β cells. Glucagon-like peptide 1 (GLP-1) treatment reduces endogenous insulin resistance in HFD-induced type 2 diabetes mellitus. In the present study, the underlying mechanism by which GLP-1 exerts its function in type 2 diabetes mellitus was investigated...
March 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28285800/perspectives-on-cardiovascular-effects-of-incretin-based-drugs-from-bedside-to-bench-return-trip
#12
Michaela Luconi, Giulia Cantini, Antonio Ceriello, Edoardo Mannucci
Recently, cardiovascular outcome trials with glucose-lowering drugs used in type 2 diabetes mellitus, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), liraglutide and semaglutide, showed a reduction in cardiovascular events, which had not been observed in trials with other incretin-based drugs, such as lixisenatide or with dipeptidyl peptidase-4 inhibitors (DPP4i). Mechanisms underlying the observed cardiovascular differences between DPP4i and GLP1-RA, and across individual GLP1-RA are poorly understood...
March 2, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28284167/albiglutide-for-the-treatment-of-type-2-diabetes-mellitus-an-integrated-safety-analysis-of-the-harmony-phase-3-trials
#13
Bo Ahrén, Molly C Carr, Karen Murphy, Christopher Perkins, Marc Rendell, Jason Mallory, Timothy Wilson, Susan Johnson
AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) stimulate the incretin system and lower glycaemic parameters in type 2 diabetes mellitus (T2DM). This analysis of clinical studies of up to 3years evaluated the safety of albiglutide, a GLP-1 RA, in people with T2DM. METHODS: Integrated safety analysis included seven phase-3 T2DM studies of albiglutide compared with placebo and/or active comparators (a dipeptidyl peptidase-4 inhibitor, GLP-1 RA, insulin, sulphonylurea, and thiazolidinedione)...
February 20, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28283573/genetically-encoded-photocrosslinkers-determine-the-biological-binding-site-of-exendin-4-in-the-n-terminal-domain-of-the-intact-human-glucagon-like-peptide-1-receptor-glp-1r
#14
Cassandra Koole, Christopher A Reynolds, Juan C Mobarec, Caroline Hick, Patrick M Sexton, Thomas P Sakmar
The glucagon-like peptide-1 receptor (GLP-1R) is a key therapeutic target in the management of type II diabetes mellitus, with actions including regulation of insulin biosynthesis and secretion, promotion of satiety and preservation of β-cell mass. Like most class B G protein-coupled receptors (GPCRs), there is limited knowledge linking biological activity of the GLP-1R with the molecular structure of an intact, full-length, functional receptor-ligand complex. In this study, we have utilized genetic code expansion to site-specifically incorporate the photoactive amino acid p-azido-L-phenylalanine (azF) into N-terminal residues of a full-length, functional human GLP-1R in mammalian cells...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28283565/assessment-of-pancreas-safety-in-the-development-program-of-once-weekly-glp-1-receptor-agonist-dulaglutide
#15
Michael A Nauck, Jean-Louis Frossard, Jamie S Barkin, Greg Anglin, Ingrid E Hensley, Kristine D Harper, Zvonko Milicevic
OBJECTIVE: To assess the risk of acute pancreatitis during treatment with glucagon-like peptide 1 receptor agonist dulaglutide, placebo, and active comparators across phase 2/3 dulaglutide trials. RESEARCH DESIGN AND METHODS: A total of 6,005 patients with type 2 diabetes participated (dulaglutide group N = 4,006 [dose range 0.1-3.0 mg]; active comparator group [metformin, sitagliptin, exenatide twice daily, insulin glargine] N = 1,541; placebo group N = 703; 245 placebo-treated patients subsequently received dulaglutide or sitagliptin and were also included in these groups) for up to 104 weeks...
March 10, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28281233/common-channel-length-in-bypass-surgery-does-not-impact-t2dm-in-diabetic-zucker-rats
#16
Claudia Laessle, Sven Michelmichel, Goran Marjanovic, Simon Kuesters, Gabriel Seifert, Ulrich T Hopt, Jodok Matthias Fink
INTRODUCTION: Metabolic surgery is known to impact glucose tolerance but the exact mechanism is still unclear. Based on recently-published data, especially the role of the hindgut may require redefinition. METHODS: Either a loop duodeno-jejunostomy (DJOS) with exclusion of one third of total intestinal length, a loop duodeno-ileostomy (DiOS, exclusion of two thirds), or SHAM operation was performed in 9-week-old Zucker diabetic fatty rats. One, 3, and 6 months after surgery, an oral glucose tolerance test (OGTT) and glucose-stimulated hormone analyses were conducted...
March 9, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28276972/pharmacotherapy-of-treatment-resistant-type-2-diabetes
#17
André J Scheen
Despite type 2 diabetes (T2D) management offers a variety of pharmacological interventions targeting different defects, numerous patients remain with persistent hyperglycaemia responsible for severe complications. Unlike resistant hypertension, treatment resistant T2D is not a classical concept although it is a rather common observation in clinical practice. Areas covered: This article proposes a definition for 'treatment resistant diabetes', analyses the causes of poor glucose control despite standard therapy, briefly considers the alternative approaches to glucose-lowering pharmacotherapy and finally describes how to overcome poor glycaemic control, using innovative oral or injectable combination therapies...
March 1, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28276830/bariatric-surgery-time-to-replace-with-glp-1
#18
Dominic-Luc Webb, Niclas Abrahamsson, Magnus Sundbom, Per M Hellström
Obesity with a body mass index (BMI) over 30 kg/m(2) represents a significant risk for increased morbidity and mortality, with reduced life expectancy of about 10 years. Until now, surgical treatment has been the only effective longterm intervention. The currently standardized method of bariatric surgery, gastric bypass, means that many gastrointestinal peptide hormones are activated, yielding net reductions in appetite and food intake. Among the most important gut peptide hormones in this perspective is glucagon-like peptide-1 (GLP-1), which rises sharply after gastric bypass...
February 24, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28276778/glp-1-receptor-agonists-in-the-treatment-of-polycystic-ovary-syndrome
#19
Elizabeth Mary Lamos, Rana Malek, Stephen N Davis
Polycystic ovarian syndrome (PCOS) affects many women of child-bearing age and is characterized by hyperandrogenism, ovulatory and metabolic dysfunction. A primary treatment goal is weight reduction. The weight loss effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), previously demonstrated in diabetic and obese non-diabetic patients, offer a unique opportunity to expand the medical options available to PCOS patients. Areas covered: Available clinical trials of glucagon-like peptide-1 receptor agonist therapy in PCOS were reviewed...
February 13, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28274625/apd668-a-g-protein-coupled-receptor-119-agonist-improves-fat-tolerance-and-attenuates-fatty-liver-in-high-trans-fat-diet-induced-steatohepatitis-model-in-c57bl-6-mice
#20
Umakant Ashok Bahirat, Rekha Raghuveer Shenoy, Rajan Naresh Goel, Kumar V S Nemmani
G-protein coupled receptor 119 (GPR119) receptor is a rhodopsin-like, class A Gαs-coupled receptor, predominantly expressed in pancreatic islet cells and intestinal entero-endocrine cells. GPR119 has been emerged as a novel therapeutic target for the treatment of dyslipidemia in type 2 diabetes. In this study, we investigated the effect of APD668, a GPR119 agonist alone and in combination with linagliptin, a DPPIV inhibitor on oral fat tolerance test. Our findings demonstrate that APD668, a GPR119 agonist inhibits the intestinal triglyceride absorption after acute fat load in mice...
March 6, 2017: European Journal of Pharmacology
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