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Glucagon like peptide 2

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https://www.readbyqxmd.com/read/29239601/preparation-and-pharmaceutical-characterizations-of-lipidated-dimeric-xenopus-glucagon-like-peptide-1-conjugates
#1
Jing Han, Feng Zhou, Yingying Fei, Xinyu Chen, Junjie Fu, Hai Qian
Two glucagon-like peptide-1 (GLP-1) analogs (1 and 2) were synthesized by hybridizing the key sequences of GLP-1, exendin-4, lixisenatide and xenGLP-1B (Xenopus GLP-1 analog). To achieve long-acting hypoglycemic effects and to further improve their antidiabetic potencies, lipidization and dimerization strategies were used to afford two lipidated dimeric conjugates (9 and 11). Conjugates 9 and 11 showed stronger receptor activation potency than GLP-1 and exendin-4 in vitro. Moreover, 9 and 11 exhibited superior hypoglycemic and insulinotropic activities to liraglutide in db/db mice...
December 14, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29236983/cardioprotective-anti-hyperglycaemic-medications-a-review-of-clinical-trials
#2
Haitham M Ahmed, Haitham Khraishah, Leslie Cho
Despite extensive clinical efforts to achieve stricter glycaemic control over the past few decades, cardiovascular (CV) disease remains the leading cause of death among diabetic patients. Recently, sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor (GLP-1-R) agonists have gained attention due to their apparent effects in reducing CV mortality. Four CV randomized controlled trials: EMPA-REG, CANVAS, LEADER, and SUSTAIN-6, found a decrease in CV events among patients with type 2 diabetes on empagliflozin, canagliflozin, liraglutide, and semaglutide, respectively...
December 9, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29235598/the-stimulation-of-glp-1-secretion-and-delivery-of-glp-1-agonists-via-nanostructured-lipid-carriers
#3
Neha Shrestha, Oriane Bouttefeux, Kevin Vanvarenberg, Patrik Lundquist, Juan Cunarro, Sulay Tovar, Georgiy Khodus, Ellen Andersson, Åsa V Keita, Carlos Gonzalez Dieguez, Per Artursson, Véronique Préat, Ana Beloqui
Nanoparticulate based drug delivery systems have been extensively studied to efficiently encapsulate and deliver peptides orally. However, most of the existing data mainly focus on the nanoparticles as a drug carrier, but the ability of nanoparticles having a biological effect has not been exploited. Herein, we hypothesize that nanostructured lipid carriers (NLCs) could activate the endogenous glucagon-like peptide-1 (GLP-1) secretion and also act as oral delivery systems for GLP-1 analogs (exenatide and liraglutide)...
December 13, 2017: Nanoscale
https://www.readbyqxmd.com/read/29231791/glucagon-like-peptide-2-and-neoplasia-a-systematic-review
#4
Linea Landgrebe Ring, Nikolaj Nerup, Palle Bekker Jeppesen, Lars Bo Svendsen, Michael Patrick Achiam
Glucagon like peptide-2 is synthesized from enteroendocrine L cells primarily located in the ileum and large intestine. GLP-2 stimulates crypt cell proliferation, increases intestinal blood flow, enhances gut barrier function, induces mucosal healing, and exerts an anti-apoptotic effect. Due to these effects GLP-2 is used in the treatment of short bowel syndrome (SBS). Areas covered The aim of this systematic review was to provide information on the potential risk of intestinal neoplasia in patients receiving treatment with GLP-2...
December 12, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29229616/glutamine-elicited-secretion-of-glucagon-like-peptide-1-glp-1-is-governed-by-an-activated-glutamate-dehydrogenase
#5
Lotta E Andersson, Liliya Shcherbina, Mahmoud Al-Majdoub, Neelanjan Vishnu, Claudia Balderas Arroyo, Jonathan Aste Carrara, Claes B Wollheim, Malin Fex, Hindrik Mulder, Nils Wierup, Peter Spégel
Glucagon-like peptide-1 (GLP-1), secreted from intestinal L-cells, glucose-dependently stimulates insulin secretion from beta-cells. This glucose-dependence prevents hypoglycemia, rendering GLP-1 analogues a useful and safe treatment modality in type-2 diabetes. While the amino acid glutamine is a potent elicitor of GLP-1 secretion, the responsible mechanism remains unclear.We investigated how GLP-1 secretion is metabolically coupled in L-cells (GLUTag) and in vivo in mice, using the insulin-secreting cell-line INS-1 832/13 as reference...
December 11, 2017: Diabetes
https://www.readbyqxmd.com/read/29228720/gastric-myoelectric-activity-during-cisplatin-induced-acute-and-delayed-emesis-reveals-a-temporal-impairment-of-slow-waves-in-ferrets-effects-not-reversed-by-the-glp-1-receptor-antagonist-exendin-9-39
#6
Zengbing Lu, Man P Ngan, Ge Lin, David T W Yew, Xiaodan Fan, Paul L R Andrews, John A Rudd
Preclinical studies show that the glucagon-like peptide-1 (GLP-1) receptor antagonist, exendin (9-39), can reduce acute emesis induced by cisplatin. In the present study, we investigate the effect of exendin (9-39) (100 nmol/24 h, i.c.v), on cisplatin (5 mg/kg, i.p.)-induced acute and delayed emesis and changes indicative of 'nausea' in ferrets. Cisplatin induced 37.2 ± 2.3 and 59.0 ± 7.7 retches + vomits during the 0-24 (acute) and 24-72 h (delayed) periods, respectively. Cisplatin also increased (P<0...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227575/effect-of-a-single-dose-of-the-dpp-4-inhibitor-sitagliptin-on-%C3%AE-cell-function-and-incretin-hormone-secretion-after-meal-ingestion-in-healthy-volunteers-and-drug-na%C3%A3-ve-well-controlled-type-2-diabetes-subjects
#7
Wathik Alsalim, Olga Göransson, Richard D Carr, Roberto Bizzotto, Andrea Tura, Giovanni Pacini, Andrea Mari, Bo Ahrén
To explore the effects of a single dose of the DPP-4 inhibitor sitagliptin on glucose-standardized insulin secretion and β-cell glucose sensitivity after meal ingestion, twelve healthy- and twelve drug naïve well-controlled type 2 diabetes subjects (T2D; mean HbA1c 43 mmol/mol, 6.2%) received sitagliptin (100mg) or placebo before a meal (525 kcal). β-cell function was measured as the insulin secretory rate at a standardized glucose concentration and the β-cell glucose sensitivity (the slope between glucose and insulin secretory rate)...
December 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29226876/serum-c-peptide-visfatin-resistin-and-ghrelin-are-altered-in-sporadic-and-grn-associated-frontotemporal-lobar-degeneration
#8
Roberta Zanardini, Luisa Benussi, Silvia Fostinelli, Claudia Saraceno, Miriam Ciani, Barbara Borroni, Alessandro Padovani, Giuliano Binetti, Roberta Ghidoni
Frontotemporal lobar degeneration (FTLD) is a group of complex neurodegenerative disease characterized by progressive deterioration of the frontal and anterior temporal lobes of the brain resulting in different heterogeneous conditions, mainly characterized by personality changes, behavioral disturbances, such as binge eating, and deficits in language and executive functions. Null mutations in progranulin gene (GRN) are one of the most frequent genetic determinants in familial frontotemporal dementia. Recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance revealing its metabolic function...
December 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226686/enhanced-specific-activity-by-multi-chelation-of-exendin-3-leads-to-improved-image-quality-and-in-vivo-beta-cell-imaging
#9
Lieke Joosten, Maarten Brom, Hanneke Peeters, Sandra Heskamp, Martin Behe, Otto C Boerman, Martin Gotthardt
OBJECTIVE: Glucagon like peptide-1 receptor (GLP-1R) targeting using radiolabeled exendin is a promising approach to non-invasively visualize and determine beta cell mass (BCM), which could help to unravel the pathophysiology of diabetes. However, saturation of the GLP-1R on beta cells occurs at low peptide doses, since the number of receptors expressed under physiological conditions is low. Therefore, tracers with high specific activities are required to sensitively image small variations in BCM...
December 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29226685/size-effect-on-lipid-nanocapsules-mediated-glp-1-secretion-from-enteroendocrine-l-cells
#10
Yining Xu, Dario Carradori, Mireille Alhouayek, Giulio G Muccioli, Patrice D Cani, Veronique Preat, Ana Beloqui
L cells are enteroendocrine cells located throughout the gastrointestinal tract that secrete physiologically important peptides. The most characterized peptides secreted by L cells are the peptide YY (PYY) and the glucagon-like peptide (GLP) -1 and -2. These peptides are released rapidly into the circulation after oral nutrient ingestion. Recently, lipid-based nanoparticles (NP) have been described as triggers for GLP-1 secretion by L cells. NP physicochemical properties play a key role in the NP-cell interaction, and drive NP cell internalization...
December 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29226618/enteroinsular-hormones-in-two-siblings-with-donohue-syndrome-and-complete-leptin-deficiency
#11
M Güemes, S A Rahman, P Shah, K Hussain
The main biochemical hallmark of the rare and lethal condition of Donohue syndrome (DS) is hyperinsulinemia. The roles of the gut and other pancreatic hormones involved in glucose metabolism, satiety and energy expenditure have not been previously reported in DS. Two siblings with genetically confirmed DS and extremely low weight underwent a mixed meal (MM) test where pancreatic hormones insulin, C-peptide, glucagon, active amylin, pancreatic polypeptide (PP) as well as gut hormones active glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), ghrelin, peptide YY (PYY) and leptin were analyzed using a Multiplex assay...
December 11, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/29225892/correlates-of-second-line-type-2-diabetes-medication-selection-in-the-usa
#12
Ronald T Ackermann, Amisha Wallia, Matthew J O'Brien, Raymond Kang, Andrew Cooper, Margaret R Moran, David T Liss
Objective: Past research provides insufficient evidence to inform second-line diabetes medication prescribing when metformin is no longer sufficient. We evaluated patient, prescriber, and health plan characteristics associated with selection of second-line diabetes medications in the USA. Research design and methods: We used a multiple case-comparison study design to identify characteristics associated with the probability of starting each of six second-line diabetes medication alternatives within 77 744 adults enrolled in commercial or Medicare Advantage health plans from 2011 to 2015...
2017: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/29225111/liraglutide-regulates-the-viability-of-pancreatic-%C3%AE-cells-and-pancreatic-%C3%AE-cells-through-camp-pka-signal-pathway
#13
Xuejuan Xu, Jinsong Chen, Lidong Hu, Ming Liang, Xiaozhou Wang, Si Feng, Jie Shen, Xiaojun Luan
AIMS: As a glucagon-like peptide-1 receptor agonist, liraglutide could effectively increase insulin secretion from pancreatic β-cells and suppress glucagon secretion from pancreatic α-cells in the treatment of hyperglycemia in type 2 diabetes patients. However, the mechanisms for the different regulation of pancreatic α-cells and β-cells are still unclear. In this study, we mainly explored the different effects of liraglutide on mouse pancreatic α-cell line and β-cell line in vitro...
December 7, 2017: Life Sciences
https://www.readbyqxmd.com/read/29221659/cardiovascular-outcomes-with-glucagon-like-peptide-1-receptor-agonists-in-patients-with-type-2-diabetes-a-meta-analysis
#14
M Angelyn Bethel, Rishi A Patel, Peter Merrill, Yuliya Lokhnygina, John B Buse, Robert J Mentz, Neha J Pagidipati, Juliana C Chan, Stephanie M Gustavson, Nayyar Iqbal, Aldo P Maggioni, Peter Öhman, Neil R Poulter, Ambady Ramachandran, Bernard Zinman, Adrian F Hernandez, Rury R Holman
BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs. Findings from cardiovascular outcome trials showed cardiovascular safety of GLP-1 receptor agonists, but results for cardiovascular efficacy were varied. We aimed to examine overall cardiovascular efficacy for lixisenatide, liraglutide, semaglutide, and extended-release exenatide. METHODS: In this systematic review and meta-analysis, we analysed data from eligible trials that assessed the safety and efficacy of GLP-1 receptor agonists compared with placebo in adult patients (aged 18 years or older) with type 2 diabetes and had a primary outcome including, but not limited to, cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke...
December 5, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/29218595/quantitative-testing-of-prescriber-knowledge-regarding-the-risks-and-safe-use-of-albiglutide
#15
Carol Koro, Janet Pientka, Veronica Bainbridge, Natalie O'Donnell, Monika Stender, Annette Stemhagen
BACKGROUND: The risk of pancreatitis and potential risk of medullary thyroid carcinoma associated with glucagon-like peptide-1 receptor agonists prompted the US Food and Drug Administration to require a Risk Evaluation and Mitigation Strategy for albiglutide, including education for prescribers and subsequent assessment of their knowledge of the risks and safe use of albiglutide via a quantitative survey. OBJECTIVE: The objective of this study was to assess prescribers' knowledge of the risks related to medullary thyroid carcinoma, pancreatitis, and the appropriate patient population for albiglutide...
December 7, 2017: Drugs—Real World Outcomes
https://www.readbyqxmd.com/read/29210642/antidiabetics-structural-diversity-of-molecules-with-a-common-aim
#16
Jelena B Popovic-Dordevic, Ivana I Jevtic, Tatjana P Stanojkovic
BACKGROUND: Diabetes mellitus type 2 (DMT2) is an endocrine disease of global proportions which is currently affecting 1 in 12 adults in the world, with still increasing prevalence. World Health Organization (WHO) declared this worldwide health problem, as an epidemic disease, to be the only non-infectious disease with such categorization. People with DMT2 are at increased risk of various complications and have shorter life expectancy. The main classes of oral antidiabetic drugs accessible today for DMT2 vary in their chemical composition, modes of action, safety profiles and tolerability...
December 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29209277/exenatide-improves-bone-quality-in-a-murine-model-of-genetically-inherited-type-2-diabetes-mellitus
#17
Marie Pereira, Stephanie Gohin, Jean-Paul Roux, Amy Fisher, Mark E Cleasby, Guillaume Mabilleau, Chantal Chenu
Type 2 diabetes mellitus (T2DM) is associated with skeletal complications, including an increased risk of fractures. Reduced blood supply and bone strength may contribute to this skeletal fragility. We hypothesized that long-term administration of Exenatide, a glucagon-like peptide-1 receptor agonist, would improve bone architecture and strength of T2DM mice by increasing blood flow to bone, thereby stimulating bone formation. In this study, we used a model of obesity and severe T2DM, the leptin receptor-deficient db/db mouse to assess alterations in bone quality and hindlimb blood flow and to examine the beneficial effects of 4 weeks administration of Exenatide...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29206832/the-effects-of-dipeptidyl-peptidase-4-inhibitors-on-bone-fracture-among-patients-with-type-2-diabetes-mellitus-a-network-meta-analysis-of-randomized-controlled-trials
#18
Jun Yang, Chao Huang, Shanshan Wu, Yang Xu, Ting Cai, Sanbao Chai, Zhirong Yang, Feng Sun, Siyan Zhan
AIM: The association between dipeptidyl peptidase-4 inhibitors (DPP-4is), a class of anti-diabetes, and bone fracture in patients with type 2 diabetes mellitus (T2DM) is unknown. This meta-analysis aimed to systematically evaluate the effects of DPP-4is on bone fracture in T2DM patients. METHODS: We searched the Cochrane Library, Embase, Medline and ClinicalTrials.gov from inception through April 28th, 2016 to identify randomized controlled trials (RCTs) that compared DPP-4is with placebo or other anti-diabetes in T2DM patients...
2017: PloS One
https://www.readbyqxmd.com/read/29205856/use-and-effectiveness-of-a-fixed-ratio-combination-of-insulin-degludec-liraglutide-ideglira-in-a-real-world-population-with-type-2-diabetes-results-from-a-european-multicentre-retrospective-chart-review-study
#19
Hermione Price, Matthias Blüher, Rudolf Prager, Tra-Mi Phan, Brian Larsen Thorsted, Bernd Schultes
AIMS: EXTRA aimed to describe real-world use and effectiveness of IDegLira, a fixed-ratio combination of the basal insulin degludec, and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide. MATERIALS AND METHODS: This European, multicentre, retrospective chart review comprised adults (n=611) with type 2 diabetes, who started IDegLira ≥6 months before data collection. Clinical characteristics were assessed at baseline (defined as the most recent recording during the 6 months before the first IDegLira prescription) and 3, 6, 9 and 12 months (± 45 days for each time point) after commencing IDegLira, where data available...
December 5, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29205117/characterization-of-optimized-functional-complementary-dual-insulinotorpic-peptide-rolgg
#20
Yaofang Zhang, Li Du, Yanling Xu, Lin Tian, Peipei Tu, Minggang Li
BACKGROUND: Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) play a similar but complementary role in the regulation of glucose levels in islet β-cells. This study was aimed to develop a fusion peptide, which combines 4 tandem repeated GLP-1 and 4 tandem repeated GIP (4rolGG), and to investigate its therapeutic effect on type 2 diabetes using a diabetic mice model. METHOD: A 4rolGG expression plasmid was constructed and expressed in BL21 (DE3)...
December 3, 2017: Current Pharmaceutical Biotechnology
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