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insulin and GLP-1 analog

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https://www.readbyqxmd.com/read/28424924/effects-of-gw002-a-novel-recombinant-human-glucagon-like-peptide-1-glp-1-analog-fusion-protein-on-cho-recombinant-cells-and-bks-db-mice
#1
Wan-Wan Ji, Dong-An Yu, Min Fan, Meng You, You Lu, Er-Bing Li, Ning Xie, Shou-Sheng Yan
AIMS: GLP-1-based strategies have many advantages in treatment of type 2 diabetes mellitus (T2DM), but native GLP-1 has a short half-life in the circulation, which limits its clinical application. The purpose of this study was to evaluate the effects of GW002, a novel recombinant GLP-1 analog fusion protein produced by linking the human GLP-1 analog C-terminus to the N-terminus of human serum albumin via a linker, in vitro and in BKS-db mice. METHODS: To determine whether GW002 can activate the GLP-1 receptor in cells, the level of luciferase expression was evaluated in vitro...
April 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28336368/novel-strategies-in-the-oral-delivery-of-antidiabetic-peptide-drugs-insulin-glp-1-and-its-analogs
#2
REVIEW
Ruba Ismail, Ildikó Csóka
As diabetes is a complex disorder being a major cause of mortality and morbidity in epidemic rates, continuous research has been done on new drug types and administration routes. Up to now, a large number of therapeutic peptides have been produced to treat diabetes including insulin, glucagon-like peptide-1 (GLP-1) and its analogs. The most common route of administration of these antidiabetic peptides is parenteral. Due to several drawbacks associated with this invasive route, delivery of these antidiabetic peptides by the oral route has been a goal of pharmaceutical technology for many decades...
March 21, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28176959/a-systematic-literature-review-on-the-efficacy-effectiveness-gap-comparison-of-randomized-controlled-trials-and-observational-studies-of-glucose-lowering-drugs
#3
REVIEW
Mikkel Z Ankarfeldt, Erpur Adalsteinsson, Rolf Hh Groenwold, M Sanni Ali, Olaf H Klungel
AIM: To identify a potential efficacy-effectiveness gap and possible explanations (drivers of effectiveness) for differences between results of randomized controlled trials (RCTs) and observational studies investigating glucose-lowering drugs. METHODS: A systematic literature review was conducted in English language articles published between 1 January, 2000 and 31 January, 2015 describing either RCTs or observational studies comparing glucagon-like peptide-1 analogs (GLP-1) with insulin or comparing dipeptidyl peptidase-4 inhibitors (DPP-4i) with sulfonylurea, all with change in glycated hemoglobin (HbA1c) as outcome...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/28176886/assessment-of-channeling-bias-among-initiators-of-glucose-lowering-drugs-a-uk-cohort-study
#4
Mikkel Z Ankarfeldt, Brian L Thorsted, Rolf Hh Groenwold, Erpur Adalsteinsson, M Sanni Ali, Olaf H Klungel
BACKGROUND: Channeling bias may occur when a newly marketed drug and an established drug, despite similar indications, are prescribed to patients with different prognostic characteristics (ie, confounding). AIM: To investigate channeling bias and its impact on relative effectiveness of glucagon-like peptide-1 (GLP-1) analogs versus basal insulin and dipeptidyl peptidase-4 inhibitors (DPP-4i) versus sulfonylurea. METHODS: In the UK Clinical Practice Research Datalink, patients with type 2 diabetes initiating treatment between 2006 and 2015 were included...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/28118069/rationale-for-treatment-options-for-mealtime-glucose-control-in-patients-with-type-2-diabetes
#5
REVIEW
Stephen L Aronoff
While glycemic control is routinely assessed using HbA1c and fasting glucose measures, postprandial glucose (PPG) is also an important contributor of overall glycemia. Furthermore, PPG excursions have been linked to complications of diabetes. This review examines the effects of glucose-lowering therapies (including treatments administered at mealtime) on postprandial hyperglycemia in patients with type 2 diabetes. A PubMed search was conducted to identify clinical studies of treatments for mealtime glucose control in type 2 diabetes...
March 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28098139/appetite-responses-to-high-fat-meals-or-diets-of-varying-fatty-acid-composition-a-comprehensive-review
#6
REVIEW
S Kaviani, J A Cooper
Dietary fatty acids (FA) act as signaling molecules with diverse effects on physiologic function. The aim of this article is to review and summarize the clinical human studies in the literature on how dietary FA composition in meals and diets affects hunger and satiety signaling in the body. Studies examining FA saturation (monounsaturated (MUFA), saturated or polyunsaturated (PUFA) FAs) or FA chain length from high-fat meals/diets were included. Measures of appetite included visual analog scale (VAS) questionnaires, appetite hormones (Cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), gastric insulinotropic polypeptide gastric inhibitory peptide (GIP), ghrelin, leptin, insulin) and/or energy intake (EI) data...
January 18, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28074109/improvement-of-quality-of-life-through-glycemic-control-by-liraglutide-a-glp-1-analog-in-insulin-naive-patients-with-type-2-diabetes-mellitus-the-page1-study
#7
Hitoshi Ishii, Tetsuji Niiya, Yasuhiro Ono, Naoyuki Inaba, Hideaki Jinnouchi, Hirotaka Watada
BACKGROUND: In addition to achieving good glycemic control, diabetes care management aims to improve the quality of life (QOL) in patients. Treatment-associated difficulties and side effects frequently cause deterioration in QOL. Liraglutide, a GLP-1 receptor agonist, is a novel injection drug that promotes insulin secretion. It is a user-friendly, once-daily injection with fewer hypoglycemic events. In this study, we aimed to examine the effect of liraglutide therapy on QOL in patients...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28043300/-influences-of-exendin-4-on-the-secretion-function-of-islet-beta-cells-from-rats-in-the-early-stage-of-severe-scald
#8
D X Zhao, L Ma, Z A Shen, D W Li, Y R Shang, K Yin, W F Cheng, X Wang, Z X Liu
Objective: To observe the secretion function changes of islet beta cells isolated from rats in the early stage of severe scald, and to explore the influence of them. Methods: Thirty-six Wistar rats were divided into sham injury (SI) group, sham injury+ exendin-4 (SIE) group, scald (S) group, and scald+ exendin-4 (SE) group according to the random number table, with 9 rats in each group. Rats in groups S and SE were inflicted with 50% total body surface area full-thickness scald by a 12-s immersion of back and a 6-s immersion of abdomen in 94 ℃ hot water...
December 20, 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28036112/protocol-of-glucose-control-safety-and-efficacy-in-type-2-diabetes-a-network-meta-analysis-glucose-dinet-protocol-rational-and-design
#9
REVIEW
Guillaume Grenet, Audrey Lajoinie, Shams Ribault, Gia Bao Nguyen, Thomas Linet, Augustin Metge, Catherine Cornu, Michel Cucherat, Philippe Moulin, François Gueyffier
The aim of this study was to propose a ranking of the currently available antidiabetic drugs, regarding vascular clinical outcomes, in patients with type 2 diabetes, through a network meta-analysis approach. Randomized clinical trials, regardless of the blinding design, testing contemporary antidiabetic drugs, and considering clinically relevant outcomes in patients with type 2 diabetes mellitus will be included. The primary outcomes of this analysis will be overall mortality, cardiovascular mortality, and major cardiovascular events...
December 30, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27965024/a-novel-glp-1-analog-a-dimer-of-glp-1-via-covalent-linkage-by-a-lysine-prolongs-the-action-of-glp-1-in-the-treatment-of-type-2-diabetes
#10
Yingying Pan, Siwei Shi, Xun Lao, Jinlong Zhang, Shiming Tan, Zirong Wu, Jing Huang
GLP-1 is an incretin hormone that can effectively lower blood glucose, however, the short time of biological activity and the side effect limit its therapeutic application. Many methods have been tried to optimize GLP-1 to extend its in vivo half-time, reduce its side effect and enhance its activity. Here we have chosen the idea to dimerize GLP-1 with a C-terminal lysine to form a new GLP-1 analog, DLG3312. We have explored the structure and the biological property of DLG3312, and the results indicated that DLG3312 not only remained the ability to activate the GLP-1R, but also strongly stimulated Min6 cell to secrete insulin...
February 2017: Peptides
https://www.readbyqxmd.com/read/27888738/oxyntomodulin-analog-and-exendin-4-derivative-lower-plasma-glucose-in-cattle
#11
S ThanThan, Y Asada, T Saito, K Ochiiwa, H Zhao, S W Naing, H Kuwayama
The present study was undertaken with the aim of examining whether and how exendin-4 (1-3) fragment, ie, Ex-4 (1-3) fragment, contributes to the regulation of glucose. An analog of oxyntomodulin (OXM) ([Gly(2), Glu(3)]-OXM), a glucagon analog ([Gly(2), Glu(3)]-glucagon), and two derivatives of Ex-4 (glucandin and [Gly(2), Glu(3)]-glucandin) were synthesized by substituting with Gly(2), Glu(3) at the N-terminuses of OXM and glucagon and/or by attaching Ex-4 (30-39) amide at the C-terminus of glucagon. Effects of these peptides on plasma insulin and glucose concentrations were investigated in cattle by conducting 3 in vivo experiments...
November 2, 2016: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/27879196/treatment-persistence-in-the-use-of-basal-insulins-in-poland-and-germany%C3%A2
#12
Wolfgang Rathmann, Marcin Czech, Edward Franek, Karel Kostev
AIMS: To compare short-term basal insulin therapy persistence and its predictors in Poland and Germany. METHODS: Persistence was defined as proportions of patients remaining on the initial basal insulin (analogs: Poland: n = 6,889, Germany: n = 454,067; neutral protamine Hagedorn (NPH) insulins: Poland: n = 50,761, Germany: n = 226,064) over 2 years based on nationwide prescription databases (LRx; IMS Health) in Poland and Germany from 2013 to 2015. Persistence was evaluated by Kaplan-Meier curves (log-rank tests)...
November 23, 2016: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27776453/individualized-patient-centered-use-of-lixisenatide-for-the-treatment-of-type-2-diabetes-mellitus
#13
REVIEW
Markolf Hanefeld, Denis Raccah, Louis Monnier
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease associated with hyperglycemia, which can lead to serious vascular complications. Current treatment guidelines place particular emphasis on personalization of therapy. Within this guidance, the use of various second-line therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), is recommended under certain circumstances. Areas covered: Factors influencing glucose homeostasis, including gastric emptying and the associated cardiovascular (CV) risk when homeostasis is not maintained, are reviewed...
March 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27562982/new-approaches-to-feline-diabetes-mellitus-glucagon-like-peptide-1-analogs
#14
REVIEW
Chen Gilor, Adam J Rudinsky, Melanie J Hall
CLINICAL RELEVANCE: Incretin-based therapies are revolutionizing the field of human diabetes mellitus (DM) by replacing insulin therapy with safer and more convenient long-acting drugs. MECHANISM OF ACTION: Incretin hormones (glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic peptide [GIP]) are secreted from the intestinal tract in response to the presence of food in the intestinal lumen. GLP-1 delays gastric emptying and increases satiety. In the pancreas, GLP-1 augments insulin secretion and suppresses glucagon secretion during hyperglycemia in a glucose-dependent manner...
September 2016: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/27436611/liraglutide-prevents-microvascular-insulin-resistance-and-preserves-muscle-capillary-density-in-high-fat-diet-fed-rats
#15
Weidong Chai, Zhuo Fu, Kevin W Aylor, Eugene J Barrett, Zhenqi Liu
Muscle microvasculature critically regulates endothelial exchange surface area to facilitate transendothelial delivery of insulin, nutrients, and oxygen to myocytes. Insulin resistance blunts insulin-mediated microvascular recruitment and decreases muscle capillary density; both contribute to lower microvascular blood volume. Glucagon-like peptide 1 (GLP-1) and its analogs are able to dilate blood vessels and stimulate endothelial cell proliferation. In this study, we aim to determine the effects of sustained stimulation of the GLP-1 receptors on insulin-mediated capillary recruitment and metabolic insulin responses, small arterial endothelial function, and muscle capillary density...
September 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27358756/safety-concerns-over-the-use-of-intestinal-permeation-enhancers-a-mini-review
#16
REVIEW
Fiona McCartney, John P Gleeson, David J Brayden
Intestinal permeation enhancers (PEs) are key components in ∼12 oral peptide formulations in clinical trials for a range of molecules, primarily insulin and glucagon-like-peptide 1 (GLP-1) analogs. The main PEs comprise medium chain fatty acid-based systems (sodium caprate, sodium caprylate, and N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC)), bile salts, acyl carnitines, and EDTA. Their mechanism of action is complex with subtle differences between the different molecules. With the exception of SNAC and EDTA, most PEs fluidize the plasma membrane causing plasma membrane perturbation, as well as enzymatic and intracellular mediator changes that lead to alteration of intestinal epithelial tight junction protein expression...
April 2016: Tissue Barriers
https://www.readbyqxmd.com/read/27313194/mechanisms-of-surgical-control-of-type-2-diabetes-glp-1-is-key-factor
#17
REVIEW
Jens Juul Holst, Sten Madsbad
GLP-1 secretion in response to meals is dramatically increased after gastric bypass operations. GLP-1 is a powerful insulinotropic and anorectic hormone, and analogs of GLP-1 are widely used for the treatment of diabetes and recently approved also for obesity treatment. It is, therefore, reasonable to assume that the exaggerated GLP-1 secretion contributes to the antidiabetic and anorectic effects of gastric bypass. Indeed, human experiments with the GLP-1 receptor antagonist, Exendin 9-39, have shown that the improved insulin secretion, which is responsible for part of the antidiabetic effect of the operation, is reduced and or abolished after GLP-1 receptor blockade...
July 2016: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/27297962/oral-2-oleyl-glyceryl-ether-improves-glucose-tolerance-in-mice-through-the-gpr119-receptor
#18
H A Hassing, M S Engelstoft, R M Sichlau, A N Madsen, J F Rehfeld, J Pedersen, R M Jones, J J Holst, T W Schwartz, M M Rosenkilde, H S Hansen
The intestinal G protein-coupled receptor GPR119 is a novel metabolic target involving glucagon-like peptide-1 (GLP-1)-derived insulin-regulated glucose homeostasis. Endogenous and diet-derived lipids, including N-acylethanolamines and 2-monoacylglycerols (2-MAG) activate GPR119. The purpose of this work is to evaluate whether 2-oleoyl glycerol (2-OG) improves glucose tolerance through GPR119, using wild type (WT) and GPR 119 knock out (KO) mice. We here show that GPR119 is essential for 2-OG-mediated release of GLP-1 and CCK from GLUTag cells, since a GPR119 specific antagonist completely abolished the hormone release...
November 12, 2016: BioFactors
https://www.readbyqxmd.com/read/27208320/glucose-variability-in-a-26-week-randomized-comparison-of-mealtime-treatment-with-rapid-acting-insulin-versus-glp-1-agonist-in-participants-with-type-2-diabetes-at-high-cardiovascular-risk
#19
(no author information available yet)
OBJECTIVE: A1C is associated with diabetes complications but does not reflect glycemic variability (GV), which may worsen outcomes by inducing inflammation, oxidative stress, and cardiac arrhythmias. We tested whether a glucagon-like peptide 1 agonist-based regimen can reduce GV and cardiometabolic risk markers while maintaining similar A1C levels in people with insulin-requiring type 2 diabetes and high cardiovascular risk. RESEARCH DESIGN AND METHODS: After run-in on metformin and basal-bolus insulin (BBI), 102 participants continued metformin and basal insulin and were randomized to exenatide dosing before the two largest meals (glucacon-like peptide-1 receptor agonist and insulin [GLIPULIN group]) or continuation of rapid-acting insulin analogs (BBI group)...
June 2016: Diabetes Care
https://www.readbyqxmd.com/read/27179248/cardiovascular-side-effects-and-insulin-secretion-after-intravenous-administration-of-radiolabeled-exendin-4-in-pigs
#20
Anneli Rydén, Görel Nyman, Lovisa Nalin, Susanne Andreasson, Olle Korsgren, Olof Eriksson, Marianne Jensen-Waern
INTRODUCTION: Radiolabeled Exendin-4, a synthetic glucagon-like peptide-1 (GLP-1) analog, is used as a tracer for diagnostic purposes of β-cells and in experimental animal research. Exendin-4 can be radiolabeled with (68)Ga, (111)In or (99m)Tc and used for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging to diagnose insulinomas, visualization of pancreatic β-cell mass and transplanted Islets of Langerhans. In humans, Exendin-4 is widely used as a therapeutic agent for treatment of type 2 diabetes (T2D)...
July 2016: Nuclear Medicine and Biology
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