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GLP-1 analogs

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https://www.readbyqxmd.com/read/27917122/glucagon-like-peptide-1-analog-liraglutide-delays-onset-of-experimental-autoimmune-encephalitis-in-lewis-rats
#1
Brian DellaValle, Gitte S Brix, Birgitte Brock, Michael Gejl, Anne M Landau, Arne Møller, Jørgen Rungby, Agnete Larsen
Introduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS) pathology and influence the susceptibility to treatment, directing attention toward anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1) family, is also anti-diabetic and weight-reducing and is, moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE)...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27888738/oxyntomodulin-analog-and-exendin-4-derivative-lower-plasma-glucose-in-cattle
#2
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
#3
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
#4
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...
November 3, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27721013/total-pyy-and-glp-1-responses-to-submaximal-continuous-and-supramaximal-sprint-interval-cycling-in-men
#5
Tom J Hazell, Hashim Islam, Jillian R Hallworth, Jennifer L Copeland
Exercise-induced changes in appetite-regulating hormones may be intensity-dependent, however a clear dose-response relationship has not been established. The purpose of this study was to examine changes in anorexigenic markers (total PYY and GLP-1) in response to rest or exercise at submaximal and supramaximal intensities. Ten active males completed four experimental sessions in randomized order: 1) Moderate intensity continuous training (MICT; 30 min cycling at 65% VO2max); 2) High intensity continuous training (HICT; 30 min cycling at 85% VO2max); 3) Sprint interval training (SIT; 6 × 30 s "all-out" cycling bouts with 4 min recovery periods); 4) Control (CTRL; no exercise)...
October 6, 2016: Appetite
https://www.readbyqxmd.com/read/27672360/glucagon-like-peptide-1-excites-firing-and-increases-gabaergic-miniature-postsynaptic-currents-mpscs-in-gonadotropin-releasing-hormone-gnrh-neurons-of-the-male-mice-via-activation-of-nitric-oxide-no-and-suppression-of-endocannabinoid-signaling-pathways
#6
Imre Farkas, Csaba Vastagh, Erzsébet Farkas, Flóra Bálint, Katalin Skrapits, Erik Hrabovszky, Csaba Fekete, Zsolt Liposits
Glucagon-like peptide-1 (GLP-1), a metabolic signal molecule, regulates reproduction, although, the involved molecular mechanisms have not been elucidated, yet. Therefore, responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the GLP-1 analog Exendin-4 and elucidation of molecular pathways acting downstream to the GLP-1 receptor (GLP-1R) have been challenged. Loose patch-clamp recordings revealed that Exendin-4 (100 nM-5 μM) elevated firing rate in hypothalamic GnRH-GFP neurons of male mice via activation of GLP-1R...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27648144/exendin-4-protects-a%C3%AE-1-42-oligomer-induced-pc12-cell-apoptosis
#7
Chen Qiu, Yan-Ping Wang, Xiao-Dong Pan, Xiao-Ying Liu, Zhou Chen, Li-Bin Liu
BACKGROUND: Type 2 diabetes mellitus (T2DM) increases the risk of developing Alzheimer's disease. Most recently, GLP-1 analogs have been shown to have a significant neuroprotective role in several neurodegenerative diseases. However, few are known on its potential mechanism. OBJECTIVE: In this study, we report the effect of exendin-4 (Ex-4), a GLP-1 receptor agonist, on amyloid-β(1-42) peptide oligomer-induced apoptosis in a PC12 neuronal cell model. METHODS: MTT, DAPI and Annexin-V/PI assays revealed that the viability of PC12 cells decreased in a dose- and time-dependent manner after exposure to amyloid-β(1-42) oligomers...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27630114/glucagon-like-peptide-1-and-its-class-b-g-protein-coupled-receptors-a-long-march-to-therapeutic-successes
#8
REVIEW
Chris de Graaf, Dan Donnelly, Denise Wootten, Jesper Lau, Patrick M Sexton, Laurence J Miller, Jung-Mo Ahn, Jiayu Liao, Madeleine M Fletcher, Dehua Yang, Alastair J H Brown, Caihong Zhou, Jiejie Deng, Ming-Wei Wang
The glucagon-like peptide (GLP)-1 receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone secreted from three major tissues in humans, enteroendocrine L cells in the distal intestine, α cells in the pancreas, and the central nervous system, which exerts important actions useful in the management of type 2 diabetes mellitus and obesity, including glucose homeostasis and regulation of gastric motility and food intake. Peptidic analogs of GLP-1 have been successfully developed with enhanced bioavailability and pharmacological activity...
October 2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/27610604/prevalent-new-user-cohort-designs-for-comparative-drug-effect-studies-by-time-conditional-propensity-scores
#9
Samy Suissa, Erica E M Moodie, Sophie Dell'Aniello
PURPOSE: Studies of the real-world comparative effectiveness of drugs conducted using computerized healthcare databases typically involve an incident new-user cohort design for head-to-head comparisons between two medications, using exclusively treatment-naïve patients. However, the desired contrast often involves one new drug compared with an older drug, of which many users of the new drug may have switched from, seriously restricting the scope of incident new-user studies. METHODS: We introduce prevalent new-user cohort designs for head-to-head comparative drug effect studies, where incident new users are scarce...
September 9, 2016: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/27574735/exenatide-regulates-substrate-preferences-through-the-p38%C3%AE-mapk-pathway-after-ischaemia-reperfusion-injury-in-a-rat-heart
#10
Aihua Zheng, Li Cao, Shu Qin, Yue Chen, Yong Li, Dongying Zhang
BACKGROUND: It is reported that glucagon-like peptide-1 (GLP-1) has direct cardioprotective effects. We hypothesise that Exenatide, a long half-life analog of GLP-1, might protect the heart against ischaemia/reperfusion (I/R) injury. In this study, the role and mechanism of Exenatide in I/R was investigated. METHODS: Two p38 MAPK isoforms, p38α or p38γ, were knocked down by recombinant adeno-associated virus (rAAV) in male Sprague-Dawley rats. Then, rats were randomly treated with Exenatide or PBS before I/R...
August 17, 2016: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/27562982/new-approaches-to-feline-diabetes-mellitus-glucagon-like-peptide-1-analogs
#11
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/27454242/the-glucagon-like-peptide-1-analog-exendin-4-antagonizes-the-effect-of-acyl-ghrelin-on-the-respiratory-exchange-ratio
#12
Shayan Abtahi, Hayley L VanderJagt, Paul J Currie
The present study investigated the interaction of hypothalamic arcuate nucleus (ArcN) ghrelin and glucagon-like peptide-1 (GLP-1) signaling on metabolic function. Using indirect calorimetry, we first showed that acylated ghrelin, administered into the ArcN, significantly increased the respiratory exchange ratio (RER) in male Sprague-Dawley rats, representing a shift in fuel utilization toward enhanced carbohydrate oxidation and reduced lipid utilization. In contrast, treatment with similar doses of des-acyl ghrelin failed to induce reliable changes in RER...
September 7, 2016: Neuroreport
https://www.readbyqxmd.com/read/27436611/liraglutide-prevents-microvascular-insulin-resistance-and-preserves-muscle-capillary-density-in-high-fat-diet-fed-rats
#13
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/27436514/effect-of-exendin-4-on-autophagy-clearance-in-beta-cell-of-rats-with-tacrolimus-induced-diabetes-mellitus
#14
Sun Woo Lim, Long Jin, Jian Jin, Chul Woo Yang
Growing evidence suggests that GLP-1 protects beta cells against various cellular injuries by modulating autophagy. In this study, we examined whether exendin-4 (Ex-4), a GLP-1 analog, had preventive effects on tacrolimus (Tac)-induced beta cell injury by improving autophagy clearance. Rats with Tac-induced diabetes mellitus exhibited increased autophagy-associated protein expression, light chain 3B levels, and autophagic vacuole numbers in pancreatic beta cells. Additionally, Tac increased autophagy in a dose- and time-dependent manner in vitro, and inhibition of autophagosome using 3-methyladenine reduced Tac-induced islet cell injury by decreasing reactive oxygen species production and apoptosis...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27412617/duodenal-jejunal-bypass-changes-the-composition-of-the-gut-microbiota
#15
Hideya Kashihara, Mitsuo Shimada, Kozo Yoshikawa, Jun Higashijima, Toshihiro Nakao, Masaaki Nishi, Chie Takasu
This study investigated the composition of the gut microbiota in rats after duodenal-jejunal bypass (DJB) in comparison to that in rats injected with a glucagon-like peptide-1 (GLP-1) receptor analog. Six male 16-week-old OLETF rats were divided into three groups: a DJB group, a sham operation group, and a daily injection with a GLP-1 receptor agonist (liraglutide) group. The gut microbiota of the three groups was analyzed at postoperative week 8 using the PCR-clone library method targeting the 16S ribosomal RNA gene...
January 2017: Surgery Today
https://www.readbyqxmd.com/read/27408779/limiting-glucocorticoid-secretion-increases-the-anorexigenic-property-of-exendin-4
#16
Shin J Lee, Katharina Diener, Sharon Kaufman, Jean-Philippe Krieger, Klaus G Pettersen, Nino Jejelava, Myrtha Arnold, Alan G Watts, Wolfgang Langhans
OBJECTIVE: Glucagon-like peptide-1 (GLP-1) analogs are attractive options for the treatment of type II diabetes and obesity because of their incretin and anorexigenic effects. Peripheral administration of the GLP-1R agonist Exendin-4 (Ex-4) also increases glucocorticoid secretion in rodents and humans, but whether the released glucocorticoids interact with Ex-4's anorexigenic effect remains unclear. METHODS: To test this, we used two experimental approaches that suppress corticosterone secretion and then assessed Ex-4 effects on eating in adult male rats...
July 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27358756/safety-concerns-over-the-use-of-intestinal-permeation-enhancers-a-mini-review
#17
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/27322963/efficacy-of-hypoglycemic-treatment-in-type-2-diabetes-stratified-by-age-or-diagnosed-age-a-meta-analysis
#18
Xiaoling Cai, Wenjia Yang, Yifei Chen, Xueying Gao, Lingli Zhou, Simin Zhang, Xueyao Han, Linong Ji
AIM: To compare the effects of blood glucose lowering regimens in groups of patients categorized by baseline age and diagnosed age. METHODS: Placebo-controlled randomized trials in type 2 diabetes patients with a study length ≥12 weeks were included. RESULTS: A total of 246 trials were included. HbA1c changes from baseline corrected by placebo were comparable in sulfonylurea treatment between older and younger patients' groups (weighted mean difference (WMD), -1...
August 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27313194/mechanisms-of-surgical-control-of-type-2-diabetes-glp-1-is-key-factor
#19
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
#20
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...
June 14, 2016: BioFactors
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