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GLP-1 analogs

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https://www.readbyqxmd.com/read/29777582/comparative-study-of-liraglutide-and-insulin-glargine-on-glycemic-control-and-pancreatic-%C3%AE-cell-function-in-db-db-mice
#1
Yanli Li, Jia Zheng, Yunfeng Shen, Wangen Li, Meimei Liu, Jun Wang, Surong Zhu, Meihua Wu
BACKGROUND The aim of this study was to compare the effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, and insulin glargine, a long-acting insulin analog, on glycemic control and pancreatic β-cell function in db/db mice. MATERIAL AND METHODS Eight-week-old male db/db mice (n=40) were divided into five groups: the vehicle-treated group (VG) (n=8); the insulin glargine-treated group (GG) (dose, 450 mg/kg) (n=8), the low-dose liraglutide-treated group (LLG) (dose, 75 μg/kg) (n=8), the mid-dose liraglutide-treated group (MLG) (150 μg/kg) (n=8), and the high-dose liraglutide-treated group (HLG) (300 μg/kg) (n=8), treated with subcutaneous injection once daily, from 8-14 weeks-of-age...
May 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29763559/long-acting-release-microspheres-containing-novel-glp-1-analog-as-an-antidiabetic-system
#2
Sida Ruan, Yuanyuan Gu, Bo Liu, Huashan Gao, Xiongwei Hu, Haiping Hao, Liang Jin, Ting Cai
Glucagon-like peptide 1 (GLP-1) has recently received significant attention as an efficacious way to treat diabetes mellitus. However, the short half-life of the peptide limits its clinical application in diabetes. In our previous study, a novel GLP-1 analog (PGLP-1) with a longer half-life was synthesized and evaluated. Herein, we prepared the PGLP-1-loaded poly(D,L-lactide-co- glycolide) microspheres to achieve long-term effects on blood glucose control. The incorporation of zinc ion into the formulation can effectively decrease the initial burst release, and a uniform drug distribution was obtained, in contrast to native PGLP-1 encapsulated microspheres...
May 15, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29746877/liraglutide-attenuates-the-migration-of-retinal-pericytes-induced-by-advanced-glycation-end-products
#3
Wen-Jian Lin, Xue-Fei Ma, Ming Hao, Huan-Ran Zhou, Xin-Yang Yu, Ning Shao, Xin-Yuan Gao, Hong-Yu Kuang
Retinal pericyte migration represents a novel mechanism of pericyte loss in diabetic retinopathy (DR), which plays a crucial role in the early impairment of the blood-retinal barrier (BRB). Glucagon-like peptide-1 (GLP-1) has been shown to protect the diabetic retina in the early stage of DR; however, the relationship between GLP-1 and retinal pericytes has not been discussed. In this study, advanced glycation end products (AGEs) significantly increased the migration of primary bovine retinal pericytes without influencing cell viability...
May 7, 2018: Peptides
https://www.readbyqxmd.com/read/29731416/interleukin-6-delays-gastric-emptying-in-humans-with-direct-effects-on-glycemic-control
#4
Louise Lang Lehrskov, Mark Preben Lyngbaek, Line Soederlund, Grit Elster Legaard, Jan Adam Ehses, Sarah Elizabeth Heywood, Nicolai Jacob Wewer Albrechtsen, Jens Juul Holst, Kristian Karstoft, Bente Klarlund Pedersen, Helga Ellingsgaard
Gastric emptying is a critical regulator of postprandial glucose and delayed gastric emptying is an important mechanism of improved glycemic control achieved by short-acting glucagon-like peptide-1 (GLP-1) analogs in clinical practice. Here we report on a novel regulatory mechanism of gastric emptying in humans. We show that increasing interleukin (IL)-6 concentrations delays gastric emptying leading to reduced postprandial glycemia. IL-6 furthermore reduces insulin secretion in a GLP-1-dependent manner while effects on gastric emptying are GLP-1 independent...
April 28, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29729352/pegylated-prodrugs-of-antidiabetic-peptides-amylin-and-glp-1
#5
Roland Böttger, Daniel Knappe, Ralf Hoffmann
Agonists of the glucagon-like peptide-1 (GLP-1) receptor and analogs of human amylin have been studied for almost two decades due to their therapeutic potential to treat diabetes mellitus and obesity. Both native peptides exhibit unfavorable pharmacokinetics. Even optimized analogs less prone to proteolysis have to be applied at least daily or once-weekly utilizing microsphere formulations or fusion to proteins. Thus, innovative approaches allowing tuning the drug levels to achieve beneficial therapeutic responses and prolonged application intervals are demanded...
May 2, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29707863/glucagon-like-peptide-1-receptor-expression-in-the-human-eye
#6
Josephine B Hebsgaard, Charles Pyke, Emre Yildirim, Lotte B Knudsen, Steffen Heegaard, Peter H Kvist
Semaglutide is a human glucagon-like peptide-1 (GLP-1) analog that is in development for the treatment of type 2 diabetes. In the pre-approval cardiovascular outcomes trial SUSTAIN 6, semaglutide was associated with a significant increase in the risk of diabetic retinopathy complications versus placebo. GLP-1 receptor (GLP-1R) expression has previously been demonstrated in the retina in animals and humans. However, antibodies used to detect expression have been documented to be non-specific and fail to detect the GLP-1R using immunohistochemistry (IHC), a problem common for many G-protein coupled receptors...
April 29, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29705602/liraglutide-attenuates-the-depressive-and-anxiety-like-behaviour-in-the-corticosterone-induced-depression-model-via-improving-hippocampal-neural-plasticity
#7
Han Weina, Niu Yuhu, Holscher Christian, Li Birong, Shen Feiyu, Wang Le
Recent studies indicate that metabolic disorders such as diabetes and obesity are a major risk factor of psychiatric diseases. This relationship opens the opportunity to develop new antidepressant drugs by repurposing antidiabetic drugs. Previous research has demonstrated that GLP-1 analogs are neuroprotective in several neurological disease models including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In addition, the GLP-1 analog liraglutide has been shown to promote neurogenesis, which is seen to play important roles in memory formation and cognitive and emotional processing...
April 26, 2018: Brain Research
https://www.readbyqxmd.com/read/29686457/initiating-titratable-fixed-ratio-combinations-of-basal-insulin-analogs-and-glucagon-like-peptide-1-receptor-agonists-what-you-need-to-know
#8
Neil Skolnik, Debbie Hinnen, Yan Kiriakov, Melissa L Magwire, John R White
IN BRIEF Titratable fixed-ratio combinations (FRCs) of a basal insulin and a glucagon-like peptide-1 (GLP-1) receptor agonist are new therapeutic options for people with type 2 diabetes. Two FRCs-insulin degludec/liraglutide and insulin glargine/lixisenatide-have been approved for use in the United States. The two components in these FRCs target different aspects of diabetes pathophysiology, working in a complementary manner to decrease blood glucose while mitigating the side effects associated with each component (hypoglycemia and weight gain with insulin and gastrointestinal side effects with GLP-1 receptor agonists)...
April 2018: Clinical Diabetes: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/29686454/safety-and-efficacy-of-insulin-degludec-liraglutide-ideglira-and-insulin-glargine-u100-lixisenatide-iglarlixi-two-novel-co-formulations-of-a-basal-insulin-and-a-glucagon-like-peptide-1-receptor-agonist-in-patients-with-diabetes-not-adequately-controlled-on
#9
Carol H Wysham, Carlos Campos, Davida Kruger
IN BRIEF Novel co-formulations of basal insulin analogs and glucagon-like peptide-1 (GLP-1) receptor agonists have provided new options for patients with type 2 diabetes who are not reaching recommended glycemic targets. The components of currently available co-formulations (insulin degludec/ liraglutide [IDegLira,] and insulin glargine U100/lixisenatide [iGlarLixi]) act synergistically to address multiple pathophysiologic defects while minimizing the side effects associated with either component when used alone...
April 2018: Clinical Diabetes: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/29671019/lixisenatide-a-novel-glp-1-analog-protects-against-cerebral-ischemia-reperfusion-injury-in-diabetic-rats
#10
Rania G Abdel-Latif, Gehan H Heeba, Ashraf Taye, Mohamed M A Khalifa
Type 2 diabetes mellitus (T2DM) is a major risk factor for ischemic stroke accompanied by vascular dysfunction and poor cerebrovascular outcome. Lixisenatide is a glucagon like peptide-1 (GLP-1) analog that is recently used for T2DM treatment with established neuroprotective properties. This study investigated and compared the neuroprotective effect of lixisenatide against glimepiride on diabetic rats subjected to global cerebral ischemia/reperfusion (I/R) injury. T2DM-induced adult male Wistar rats were administered lixisenatide or glimepiride prior to induction of global cerebral I/R-induced injury...
April 18, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29659121/glucagon-like-peptide-1-ameliorates-cardiac-lipotoxicity-in-diabetic-cardiomyopathy-via-the-ppar%C3%AE-pathway
#11
Lujin Wu, Ke Wang, Wei Wang, Zheng Wen, Peihua Wang, Lei Liu, Dao Wen Wang
Lipotoxicity cardiomyopathy is the result of excessive accumulation and oxidation of toxic lipids in the heart. It is a major threat to patients with diabetes. Glucagon-like peptide-1 (GLP-1) has aroused considerable interest as a novel therapeutic target for diabetes mellitus because it stimulates insulin secretion. Here, we investigated the effects and mechanisms of the GLP-1 analog exendin-4 and the dipeptidyl peptidase-4 inhibitor saxagliptin on cardiac lipid metabolism in diabetic mice (DM). The increased myocardial lipid accumulation, oxidative stress, apoptosis, and cardiac remodeling and dysfunction induced in DM by low streptozotocin doses and high-fat diets were significantly reversed by exendin-4 and saxagliptin treatments for 8 weeks...
April 16, 2018: Aging Cell
https://www.readbyqxmd.com/read/29626232/a-pre-meal-of-whey-proteins-induces-differential-effects-on-glucose-and-lipid-metabolism-in-subjects-with-the-metabolic-syndrome-a-randomised-cross-over-trial
#12
Ann Bjørnshave, Jens Juul Holst, Kjeld Hermansen
PURPOSE: Postprandial lipaemia (PPL), an independent risk factor for cardiovascular disease, is affected by composition and timing of meals. We evaluated if whey proteins (WP) consumed as a pre-meal before a fat-rich meal reduce postprandial triglyceride (TG) and apolipoprotein B-48 (ApoB-48) responses in subjects with the metabolic syndrome (MeS). METHODS: An acute, randomised, cross-over trial was conducted. 20 subjects with MeS consumed a pre-meal of 0, 10 or 20 g WP 15 min prior to a fat-rich meal...
April 6, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/29593427/glucagon-like-peptide-1-exerts-anti-inflammatory-effects-on-mouse-colon-smooth-muscle-cells-through-the-cyclic-adenosine-monophosphate-nuclear-factor-%C3%AE%C2%BAb-pathway-in-vitro
#13
Ahmed Al-Dwairi, Tamara E Alqudah, Othman Al-Shboul, Mohammad Alqudah, Ayman G Mustafa, Mahmoud A Alfaqih
Background: Intestinal smooth muscle cells (SMCs) undergo substantial morphological, phenotypic, and contractile changes during inflammatory bowel disease (IBD). SMCs act as a source and target for different inflammatory mediators, however their role in IBD pathogenesis is usually overlooked. Glucagon-like peptide-1 (GLP-1) is an incretin hormone reported to exert multiple anti-inflammatory effects in different tissues including the gastrointestinal tract through various mechanisms. Aim: The aim of this research is to explore the effect of GLP-1 analog exendin-4 on the expression and secretion of inflammatory markers from mouse colon smooth muscle cells (CSMCs) after stimulation with lipopolysaccharide (LPS)...
2018: Journal of Inflammation Research
https://www.readbyqxmd.com/read/29556215/clinical-and-physiological-characterization-of-elevated-plasma-glucagon-like-peptide-1-levels-hyperglipemia-in-a-dipeptidyl-peptidase-iv-mutation-carrier
#14
Dandan Zhao, Shaoqian Zhao, Xiao Wang, Mingbo Su, Wen Liu, Qinyun Ma, Jie Hong, Weiqiong Gu, Jingya Li, Ruixin Liu, Guang Ning, Jiqiu Wang, Yifei Zhang
The clinical application of dipeptidyl peptidase IV inhibitors (DPP4i) increasing active glucagon-like peptide-1 (AGLP-1) levels has been linked to pancreatitis, pancreatic tumors, and cardiovascular events. However, DPP4 mutations in humans or the long-term outcomes of high glucagon-like peptide-1 (GLP-1) level exposure have not been reported. A trio family with a proband showing an extremely high AGLP-1 level [defined here as hyperglipemia (hyper-glucagon-like peptide-1-emia)] were conducted whole-exome sequencing for potential pathogenic genetic defects...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29545266/native-oxyntomodulin-has-significant-glucoregulatory-effects-independent-of-weight-loss-in-obese-humans-with-and-without-type-2-diabetes
#15
Sudha S Shankar, R Ravi Shankar, Lori A Mixson, Deborah L Miller, Barnali Pramanik, Amy K O'Dowd, Donna M Williams, Clay B Frederick, Chan R Beals, S Aubrey Stoch, Helmut O Steinberg, David E Kelley
Oxyntomodulin (OXM), an enteroendocrine hormone, causes appetite suppression, increased energy expenditure, and weight loss in obese humans via activation of GLP-1 and glucagon receptors. However, the effects of OXM on glucose homeostasis remain ill defined. To address this gap, we evaluated the effects of an i.v. infusion of native OXM on insulin secretion rates (ISRs) and glycemic excursion in a graded glucose infusion (GGI) procedure in two separate randomized, placebo (PBO)-controlled, single-dose crossover trials in 12 overweight and obese subjects without diabetes and in 12 obese subjects with type 2 diabetes mellitus (T2DM), using the GLP-1 analog liraglutide (LIRA) as a comparator in T2DM...
June 2018: Diabetes
https://www.readbyqxmd.com/read/29530599/the-glucagon-like-peptide-1-glp-1-analog-liraglutide-attenuates-renal-fibrosis
#16
Ya-Kun Li, Dong-Xia Ma, Zhi-Min Wang, Xiao-Fan Hu, Shang-Lin Li, Hong-Zhe Tian, Meng-Jun Wang, Yan-Wen Shu, Jun Yang
Renal fibrosis is recognized as the common route of all chronic kidney disease (CKD) progressing to end-stage renal disease (ESRD). Additionally, accumulating evidence suggests that epithelial-mesenchymal transition (EMT) plays a significant role in the process of renal fibrogenesis. Liraglutide is a long-acting glucagon-like peptide-1 (GLP-1) analog that has been widely used to treat type 2 diabetes. Recent studies have demonstrated that the GLP-1 analogs could also exert protective effects in cardiac fibrosis models...
May 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29488276/allelic-variant-in-the-glucagon-like-peptide-1-receptor-gene-associated-with-greater-effect-of-liraglutide-and-exenatide-on-gastric-emptying-a-pilot-pharmacogenetics-study
#17
V Chedid, P Vijayvargiya, P Carlson, K Van Malderen, A Acosta, A Zinsmeister, M Camilleri
BACKGROUND: Weight loss in response to the long-acting GLP-1 receptor (GLP1R) analog, liraglutide, is correlated with delay in gastric-emptying (GE). The aim of this pilot study was to assess whether specific genetic variants in GLP1R or TCF7L2 are associated with delayed GE and weight loss in obese patients treated with liraglutide or the short-acting GLP-1 agonist, exenatide. METHODS: We evaluated in obese individuals the associations of genetic variations of GLP1R (rs6923761) and TCF7L2 (rs7903146) on GE T1/2 and weight from two trials that evaluated separately exenatide, 5 μg BID for 30 days, or liraglutide, 3 mg daily for 5 weeks...
February 28, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29435980/the-diabetes-drug-liraglutide-reverses-cognitive-impairment-in-mice-and-attenuates-insulin-receptor-and-synaptic-pathology-in-a-non-human-primate-model-of-alzheimer-s-disease
#18
Andre F Batista, Leticia Forny-Germano, Julia R Clarke, Natalia M Lyra E Silva, Jordano Brito-Moreira, Susan E Boehnke, Andrew Winterborn, Brian C Coe, Ann Lablans, Juliana F Vital, Suelen A Marques, Ana Mb Martinez, Matthias Gralle, Christian Holscher, William L Klein, Jean-Christophe Houzel, Sergio T Ferreira, Douglas P Munoz, Fernanda G De Felice
Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling...
May 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29412819/gut-hormone-polyagonists-for-the-treatment-of-type-2-diabetes
#19
Sara J Brandt, Anna Götz, Matthias H Tschöp, Timo D Müller
Chemical derivatives of the gut-derived peptide hormone glucagon-like peptide 1 (GLP-1) are among the best-in-class pharmacotherapies to treat obesity and type 2 diabetes. However, GLP-1 analogs have modest weight lowering capacity, in the range of 5-10%, and the therapeutic window is hampered by dose-dependent side effects. Over the last few years, a new concept has emerged: combining the beneficial effects of several key metabolic hormones into a single molecular entity. Several unimolecular GLP-1-based polyagonists have shown superior metabolic action compared to GLP-1 monotherapies...
February 2018: Peptides
https://www.readbyqxmd.com/read/29406841/slow-titration-and-delayed-intensification-of-basal-insulin-among-patients-with-type-2-diabetes
#20
Michelle Mocarski, Jason Yeaw, Victoria Divino, Mitch DeKoven, German Guerrero, Jakob Langer, Brian Larsen Thorsted
BACKGROUND: Clinical inertia in type 2 diabetes mellitus (T2DM) refers to the failure of clinicians to intensify therapy when indicated. Many T2DM patients remain suboptimally controlled after initiating basal insulin. OBJECTIVE: To examine the prevalence of patients treated with basal insulin but in poor glycemic control (hemoglobin A1c [A1c] ≥ 7%) after initiation and subsequent treatment intensification patterns and glycemic outcomes in a real-world setting...
April 2018: Journal of Managed Care & Specialty Pharmacy
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