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GLP-1 analogs

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https://www.readbyqxmd.com/read/28300673/semi-microbiological-synthesis-of-an-active-lysinoalanine-bridged-analog-of-glucagon-like-peptide-1
#1
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/28295000/current-status-of-radiopharmaceuticals-for-the-theranostics-of-neuroendocrine-neoplasms
#2
REVIEW
Melpomeni Fani, Petra Kolenc Peitl, Irina Velikyan
Nuclear medicine plays a pivotal role in the management of patients affected by neuroendocrine neoplasms (NENs). Radiolabeled somatostatin receptor analogs are by far the most advanced radiopharmaceuticals for diagnosis and therapy (radiotheranostics) of NENs. Their clinical success emerged receptor-targeted radiolabeled peptides as an important class of radiopharmaceuticals and it paved the way for the investigation of other radioligand-receptor systems. Besides the somatostatin receptors (sstr), other receptors have also been linked to NENs and quite a number of potential radiolabeled peptides have been derived from them...
March 15, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28276830/bariatric-surgery-time-to-replace-with-glp-1
#3
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/28245463/protective-effects-of-glucagon-like-peptide-1-analog-on-renal-tubular-injury-in-mice-on-high-fat-diet
#4
Honglei Guo, Hongmei Li, Bin Wang, Wei Ding, Lilu Ling, Min Yang, Yong Gu, Jianying Niu
AIMS: The study aimed to investigate the renoprotective effect of glucagon-like peptide-1 (GLP-1) against renal tubular injury in C57BL/6 mice induced by a high-fat diet (HFD). METHODS: Twenty C57BL/6 mice were fed HFD for 12 weeks. Ten of these mice were treated with GLP-1 at 200 µg/kg subcutaneously twice daily for 4 weeks (HFDG group), and the other ten mice received vehicle only (HFD group). Ten mice fed standard rodent chow served as controls (Con group). Body weight, kidney weight, food intake, and systolic blood pressure were measured...
February 28, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28215540/decreased-glucagon-like-peptide-1-correlates-with-abdominal-pain-in-patients-with-constipation-predominant-irritable-bowel-syndrome
#5
Zheng-Yang Li, Na Zhang, Shuang Wen, Jing Zhang, Xiu-Li Sun, Xiao-Ming Fan, Yong-Hong Sun
BACKGROUND AND OBJECTIVE: The glucagon-like peptide-1 (GLP-1) analog, ROSE-010, plays a critical role in alleviating abdominal pain in patients with irritable bowel syndrome (IBS); however, the underling mechanism is unclear. In the present study, we determined the serum GLP-1 level in patients with constipation-predominant IBS (IBS-C). The relationship between GLP-1 and abdominal pain was investigated. In addition, the expression of the GLP-1 receptor in the colon was determined. METHODS: Rectosigmoid biopsies were gathered from 38 patients with IBS-C who met the Rome III criteria, and 22 healthy controls...
February 16, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28194113/cardiovascular-benefits-of-native-glp-1-and-its-metabolites-an-indicator-for-glp-1-therapy-strategies
#6
REVIEW
Junfeng Li, Juan Zheng, Susanne Wang, Harry K Lau, Ali Fathi, Qinghua Wang
Cardiovascular disease is a common co-morbidity and leading cause of death in patients with type 2 diabetes mellitus (T2DM). Glucagon-like peptide 1 (GLP-1) is a peptide hormone produced by intestinal L cells in response to feeding. Native GLP-1 (7-36) amide is rapidly degraded by diaminopeptidyl peptidase-4 (DPP4) to GLP-1 (9-36) amide, making 9-36a the major circulating form. While it is 7-36a, and not its metabolites, which exerts trophic effects on islet β-cells, recent studies suggest that both 7-36a and its metabolites have direct cardiovascular effects, including preserving cardiomyocyte viability, ameliorating cardiac function, and vasodilation...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28193513/the-importance-of-the-gastrointestinal-tract-in-controlling-food-intake-and-regulating-energy-balance
#7
M P Monteiro, R L Batterham
The gastrointestinal (GI) tract, the key interface between ingested nutrients and the body, plays a critical role in regulating energy homeostasis. Gut-derived signals convey information regarding incoming nutrients to the brain, initiating changes in eating behavior and energy expenditure, to maintain energy balance. Here we review hormonal, neural and nutrient signals emanating from the GI tract and evidence for their role in controlling feeding behavior. Mechanistic studies that have utilized pharmacological and/or transgenic approaches targeting an individual hormone/mediator have yielded somewhat disappointing bodyweight changes, often leading to the hormone/mediator in question being dismissed as a potential obesity therapy...
February 10, 2017: Gastroenterology
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
#8
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
#9
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
#10
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...
January 24, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28106956/comparisons-of-weight-changes-between-sglt2-inhibitors-treatment-and-glp-1-analogs-treatment-in-type-2-diabetes-patients-a-meta-analysis
#11
REVIEW
Xiaoling Cai, Liwei Ji, Yifei Chen, Wenjia Yang, Lingli Zhou, Xueyao Han, Simin Zhang, Linong Ji
To evaluate the efficacy of weight changes from baseline of the SGLT2 inhibitors treatment and GLP-1 analogs treatment after comparisons with placebo in type 2 diabetes patients and the associated factors MATERIALS AND METHODS: Studies were searched from when recording began, June 2004, until June 2015, and re-searched on July 2016, and placebo-controlled randomized trials in type 2 diabetes patients with a study length ≥12 weeks were included RESULTS: A total of 97 RCTs were included. Compared with placebo, treatment with SGLT2 inhibitors was associated with a significant greater decrease in weight change from baseline, (weighted mean differences (WMD), -2...
January 20, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28098139/appetite-responses-to-high-fat-meals-or-diets-of-varying-fatty-acid-composition-a-comprehensive-review
#12
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
#13
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
#14
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
#15
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/27990119/oral-administration-of-sitagliptin-activates-creb-and-is-neuroprotective-in-murine-model-of-brain-trauma
#16
Brian DellaValle, Gitte S Brix, Birgitte Brock, Michael Gejl, Jørgen Rungby, Agnete Larsen
Introduction: Traumatic brain injury is a major cause of mortality and morbidity. We have previously shown that the injectable glucagon-like peptide-1 (GLP-1) analog, liraglutide, significantly improved the outcome in mice after severe traumatic brain injury (TBI). In this study we are interested in the effects of oral treatment of a different class of GLP-1 based therapy, dipeptidyl peptidase IV (DPP-IV) inhibition on mice after TBI. DPP-IV inhibitors reduce the degradation of endogenous GLP-1 and extend circulation of this protective peptide in the bloodstream...
2016: Frontiers in 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
#17
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/27957723/low-kidney-uptake-of-glp-1r-targeting-beta-cell-specific-pet-tracer-18-f-labeled-nle-14-lys-40-exendin-4-analog-shows-promise-for-clinical-imaging
#18
Kirsi Mikkola, Cheng-Bin Yim, Paula Lehtiniemi, Saila Kauhanen, Miikka Tarkia, Tuula Tolvanen, Pirjo Nuutila, Olof Solin
BACKGROUND: Several radiometal-labeled, exendin-based tracers that target glucagon-like peptide-1 receptors (GLP-1R) have been intensively explored for β cell imaging. The main obstacle has been the high uptake of tracer in the kidneys. This study aimed to develop a novel GLP1-R-specific tracer, with fluorine-18 attached to exendin-4, to label β cells for clinical imaging with PET (positron emission tomography). We hypothesized that this tracer would undergo reduced kidney uptake. (18)F-labeled [Nle(14),Lys(40)]exendin-4 analog ([(18)F]exendin-4) was produced via Cu-catalyzed click chemistry...
December 2016: EJNMMI Research
https://www.readbyqxmd.com/read/27928844/glucagon-like-peptide-1-receptor-expression-on-human-eosinophils-and-its-regulation-of-eosinophil-activation
#19
P D Mitchell, B M Salter, J P Oliveria, A El-Gammal, D Tworek, S G Smith, R Sehmi, G M Gauvreau, M Butler, P M O'Byrne
BACKGROUND: Glucagon-like peptide-1 (GLP-1) and its receptor are part of the incretin family of hormones that regulate glucose metabolism. GLP-1 also has immune modulatory roles. OBJECTIVES: To measure the expression of the GLP-1 receptor (GLP-1R) on eosinophils and neutrophils in normal and asthmatic subjects and evaluate effects of a GLP-1 analog on eosinophil function. METHODS: Peripheral blood samples were taken from 10 normal and 10 allergic asthmatic subjects...
December 8, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27917122/glucagon-like-peptide-1-analog-liraglutide-delays-onset-of-experimental-autoimmune-encephalitis-in-lewis-rats
#20
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
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