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GLP-1 Analogues

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https://www.readbyqxmd.com/read/28209419/a-safety-and-pharmacokinetic-dosing-study-of-glucagon-like-peptide-2-in-infants-with-intestinal-failure
#1
David L Sigalet, Mary E Brindle, Dana Boctor, Bryan Dicken, Viona Lam, Lily Sia Lu, Elaine de Heuvel, Bolette Hartmann, Jens J Holst
BACKGROUND & AIMS: Glucagon-like peptide 2 (GLP-2) analogues are approved for adults with intestinal failure (IF), but no studies have included infants. This study examined the pharmacokinetics (PK), safety, and nutritional effects of GLP-2 in infants with IF. METHODS: With parental consent (Health Canada Protocol:150,979), parenteral nutrition (PN)-dependent infants were treated with 5-20-μg/kg/day GLP-2 for 3days (phase 1), and if tolerated continued for 42days (phase 2)...
January 29, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28204823/incretins-amplify-tnf-%C3%AE-stimulated-il-6-synthesis-in-osteoblasts-suppression-of-the-i%C3%AE%C2%BAb-nf-%C3%AE%C2%BAb-pathway
#2
Kazuhiko Fujita, Haruhiko Tokuda, Naohiro Yamamoto, Shingo Kainuma, Tetsu Kawabata, Go Sakai, Gen Kuroyanagi, Rie Matsushima-Nishiwaki, Atsushi Harada, Osamu Kozawa, Takanobu Otsuka
Incretins including glucagon-like peptide-1 (GLP-1) and glucose‑dependent insulinotropic polypeptide (GIP) secreted from the small intestine after oral food ingestion are currently recognized to stimulate insulin secretion from pancreatic β cells. We previously reported that p70 S6 kinase limits the tumor necrosis factor‑α (TNF‑α)‑stimulated interleukin-6 (IL‑6) synthesis in osteoblast‑like MC3T3‑E1 cells. In the present study, we investigated the effects of incretins on the TNF‑α‑induced IL‑6 synthesis and the underlying mechanism in MC3T3‑E1 cells...
February 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28161303/comparison-of-exenatide-and-acarbose-on-intra-abdominal-fat-content-in-patients-with-obesity-and-type-2-diabetes-a-randomized-controlled-trial
#3
Li Shi, Jing Zhu, Ping Yang, Xiaoqiang Tang, Wenlong Yu, Changjie Pan, Moyu Shen, Dalong Zhu, Jinluo Cheng, Xinhua Ye
OBJECTIVE: To investigate exenatide, a GLP-1 analogue, compared with acarbose, for intra-abdominal fat reduction in patients with obesity and type-2 diabetes. METHODS: This randomized controlled trial included 36 patients with obesity and type-2 diabetes, who were metformin-unresponsive, receiving metformin/exenatide (GLP-1 group) or metformin/acarbose (control group) for 3 months. Primary end-point: intra-abdominal fat content from baseline to 3 months; Secondary end-points: changes in fasting blood glucose, glycated haemoglobin (HbAlc), fasting insulin, blood lipids, weight, body mass index, and inflammatory cytokines from baseline to 3 months...
February 1, 2017: Obesity Research & Clinical Practice
https://www.readbyqxmd.com/read/28154977/sex-differences-in-the-response-of-total-pyy-and-glp-1-to-moderate-intensity-continuous-and-sprint-interval-cycling-exercise
#4
Tom J Hazell, Logan K Townsend, Jillian R Hallworth, Jon Doan, Jennifer L Copeland
BACKGROUND: Exercise interventions are often less effective at improving body composition for females than males, potentially due to post-exercise hormonal responses that increase energy intake in females. Recently, sprint interval training was shown to effectively reduce body fat in females despite being relatively low during exercise energy expenditure. PURPOSE: To determine whether any sex difference in total PYY, GLP-1 or perceived hunger exists following moderate-intensity continuous exercise (MICT) and sprint interval exercise (SIT) METHODS: Twenty-one active participants (11 females) participated in three sessions in a randomized crossover design: (1) MICT, 30-min cycling at 65% VO2max; (2) SIT, 6 × 30 s "all-out" sprints with 4-min recovery periods; (3) control (CTRL; no exercise)...
February 2, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28152036/bioactivity-of-a-modified-human-glucagon-like-peptide-1
#5
Fangfang Xu, Kevin Yueju Wang, Nan Wang, Gangqiang Li, Dehu Liu
Diabetes has become the third largest cause of death in humans worldwide. Therefore, effective treatment for this disease remains a critical issue. Glucagon-like peptide-1 (GLP-1) plays an important role in glucose homeostasis, and therefore represents a promising candidate to use for the treatment of diabetes. Native GLP-1, however, is quickly degraded in in the circulatory system; which limits its clinical application. In the present study, a chemically-synthesized, modified analogue of human GLP-1 (mGLP-1) was designed...
2017: PloS One
https://www.readbyqxmd.com/read/28145471/synergistic-effects-of-metformin-with-liraglutide-against-endothelial-dysfunction-through-glp-1-receptor-and-pka-signalling-pathway
#6
Jing Ke, Ye Liu, Jin Yang, Ran Lu, Qing Tian, Wenfang Hou, Guang Wang, Rui Wei, Tianpei Hong
Metformin or glucagon-like peptide-1 (GLP-1) analogue liraglutide has cardiovascular benefits. However, it is not clear whether their combined treatment have additive or synergistic effects on the vasculature. In this study, human umbilical vein endothelial cells (HUVECs), exposed to palmitic acid (PA) to induce endothelial dysfunction, were incubated with metformin, liraglutide or their combination. High fat diet (HFD)-fed ApoE(-/-) mice were randomized into control, metformin, liraglutide, and combination treatment groups...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28127745/5-fluorouracil-causes-endothelial-cell-senescence-potential-protective-role-of-glucagon-like-peptide-1
#7
Paola Altieri, Roberto Murialdo, Chiara Barisione, Edoardo Lazzarini, Silvano Garibaldi, Patrizia Fabbi, Clarissa Ruggeri, Silvia Borile, Federico Carbone, Andrea Armirotti, Marco Canepa, Alberto Ballestrero, Claudio Brunelli, Fabrizio Montecucco, Pietro Ameri, Paolo Spallarossa
BACKGROUND AND PURPOSE: 5-fluorouracil (5FU) and its prodrug, capecitabine, can damage endothelial cells, whilst endothelial integrity is preserved by glucagon-like peptide 1 (GLP-1). Here, we studied the effect of 5FU on endothelial senescence and whether GLP-1 antagonizes it. EXPERIMENTAL APPROACH: EA.hy926 cells were exposed to 5FU or sera from patients taking capecitabine, with or without pre-incubation with GLP-1. Senescence was identified by expression of senescence-associated β-galactosidase and p16(INK4a) and reduced cell proliferation...
January 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28115493/esculentin-2cha-1-30-and-its-analogues-stability-and-mechanisms-of-insulinotropic-action
#8
Srividya Vasu, Mary K McGahon, R Charlotte Moffett, Tim M Curtis, J Michael Conlon, Yasser H A Abdel-Wahab, Peter R Flatt
The insulin-releasing effects, cellular mechanisms of action and anti-hyperglycaemic activity of 10 analogues of esculentin-2CHa lacking the cyclic C-terminal domain (CKISKQC) were evaluated. Analogues of the truncated peptide, esculentin-2CHa(1-30), were designed for plasma enzyme resistance and increased biological activity. Effects of those analogues on insulin release, cell membrane integrity, membrane potential, intracellular Ca(2+) and cAMP levels were determined using clonal BRIN-BD11 cells. Their acute effects on glucose tolerance were investigated using NIH Swiss mice...
March 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28110911/efficacy-and-safety-of-once-weekly-semaglutide-monotherapy-versus-placebo-in-patients-with-type-2-diabetes-sustain-1-a-double-blind-randomised-placebo-controlled-parallel-group-multinational-multicentre-phase-3a-trial
#9
Christopher Sorli, Shin-Ichi Harashima, George M Tsoukas, Jeffrey Unger, Julie Derving Karsbøl, Thomas Hansen, Stephen C Bain
BACKGROUND: Despite a broad range of pharmacological options for the treatment of type 2 diabetes, optimum glycaemic control remains challenging for many patients and new therapies are necessary. Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue in phase 3 development for type 2 diabetes. We assessed the efficacy, safety, and tolerability of semaglutide monotherapy, compared with placebo, in treatment-naive patients with type 2 diabetes who had insufficient glycaemic control with diet and exercise alone...
January 16, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28057699/glucagon-like-peptide-1-and-its-analogues-act-in-the-dorsal-raphe-and-modulate-central-serotonin-to-reduce-appetite-and-body-weight
#10
Rozita H Anderberg, Jennifer E Richard, Kim Eerola, Lorena Lopez Ferreras, Elin Banke Nordbeck, Caroline Hansson, Hans Nissbrandt, Filip Berqquist, Fiona M Gribble, Frank Reimann, Ingrid Wernstedt-Asterholm, Christophe Lamy, Karolina P Skibicka
Glucagon-like peptide-1 (GLP-1) and serotonin play critical roles in energy balance regulation. Both systems are exploited clinically as anti-obesity strategies. Surprisingly whether they interact in order to regulate energy balance is poorly understood. Here we investigated mechanisms by which GLP-1 and serotonin interact at the level of the CNS. Serotonin depletion impaired the ability of exendin-4, a clinically utilized GLP-1 analogue, to reduce body weight in rats, suggesting serotonin is a critical mediator of the energy balance impact of GLP-1R activation...
January 5, 2017: Diabetes
https://www.readbyqxmd.com/read/28049736/glp-1-analogue-induced-weight-loss-does-not-improve-obesity-induced-at-dysfunction
#11
Emilie Pastel, Laura J McCulloch, Rebecca Ward, Shivam Joshi, Kim M Gooding, Angela C Shore, Katarina Kos
Glucagon-like peptide-1 (GLP-1) analogues aid weight loss which improves obesity-associated adipose tissue (AT) dysfunction. GLP-1 treatment may however also directly influence AT which expresses GLP-1 receptors. This study aimed to assess the impact of GLP-1 analogue treatment on subcutaneous AT inflammatory and fibrotic responses, compared to weight loss by calorie reduction (control). Among the 39 participants with type 2 diabetes recruited, 30 age-matched participants were randomised to 4 months treatment with Liraglutide (n=22) or calorie restriction-based on dietetic counselling (n=8)...
January 3, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28031776/glucagon-like-peptide-1-in-the-pathophysiology-and-pharmacotherapy-of-clinical-obesity
#12
REVIEW
Ananthi Anandhakrishnan, Márta Korbonits
Though the pathophysiology of clinical obesity is undoubtedly multifaceted, several lines of clinical evidence implicate an important functional role for glucagon-like peptide 1 (GLP-1) signalling. Clinical studies assessing GLP-1 responses in normal weight and obese subjects suggest that weight gain may induce functional deficits in GLP-1 signalling that facilitates maintenance of the obesity phenotype. In addition, genetic studies implicate a possible role for altered GLP-1 signalling as a risk factor towards the development of obesity...
December 15, 2016: World Journal of Diabetes
https://www.readbyqxmd.com/read/28008585/glucagon-like-peptide-1-analogues-inhibit-proliferation-and-increase-apoptosis-of-human-prostate-cancer-cells-in-vitro
#13
X-N Li, H-M Bu, X-H Ma, Sh Lu, Sh Zhao, Y-L Cui, J Sun
Background: Research has shown that the incidence of prostate cancer is increased in patients with type 2 diabetes mellitus (T2DM) 1. Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone that enhances glucose-dependent insulin secretion and suppresses glucagon release. Method: Here, we examined the effect of exenatide and liraglutide, 2 types of GLP-1 analogues, on prostate cancer cells growth by CCK-8 assay, Hoechst33258 staining assay, and western blot analysis of apoptosis-related proteins Bax and Bcl-2...
December 22, 2016: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28007055/physiological-and-pathophysiological-aspects-of-incretin-hormones-and-glucagon
#14
Jonatan Ising Bagger
Infusion of oxyntomodulin and the separate and combined infusion of GLP-1 and glucagon inhibited food intake similarly in healthy individuals, with no superior effect of combining GLP-1 and glucagon. We confirm the inhibitory effects of oxyntomodulin and GLP-1, respectively, on GE and appetite scores observed previously, but by adding glucagon to the infusion of GLP-1 we found no additive effects. Unexpectedly, glucagon alone had no effect on GE and appetite scores, but inhibited food intake to the same extent as oxyntomodulin, GLP-1 and GLP-1 + glucagon...
January 2017: Danish Medical Journal
https://www.readbyqxmd.com/read/28005376/neoglycolipids-for-prolonging-the-effects-of-peptides-self-assembling-glucagon-like-peptide-1-analogues-with-albumin-binding-properties-and-potent-in-vivo-efficacy
#15
Søren B van Witteloostuijn, Karin Mannerstedt, Pernille Wismann, Esben M Bech, Mikkel B Thygesen, Niels Vrang, Jacob Jelsing, Knud J Jensen, Søren L Pedersen
Novel principles for optimizing the properties of peptide-based drugs are needed in order to leverage their full pharmacological potential. We present the design, synthesis, and evaluation of a library of neoglycolipidated glucagon-like peptide 1 (GLP-1) analogues, which are valuable drug candidates for treatment of type 2 diabetes and obesity. Neoglycolipidation of GLP-1 balanced the lipophilicity, directed formation of soluble oligomers, and mediated albumin binding. Moreover, neoglycolipidation did not compromise bioactivity, as in vitro potency of neoglycolipidated GLP-1 analogues was maintained or even improved compared to native GLP-1...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27998088/a-ph-induced-switch-in-human-glucagon-like-peptide-1-aggregation-kinetics
#16
Karolina L Zapadka, Frederik J Becher, Shahid Uddin, Paul G Varley, Steve Bishop, A L Gomes Dos Santos, Sophie E Jackson
Aggregation and amyloid fibril formation of peptides and proteins is a widespread phenomenon. It has serious implications in a range of areas from biotechnological and pharmaceutical applications to medical disorders. The aim of this study was to develop a better understanding of the mechanism of aggregation and amyloid fibrillation of an important pharmaceutical, human glucagon-like peptide-1 (GLP-1). GLP-1 is a 31-residue hormone peptide that plays an important role regulating blood glucose levels, analogues of which are used for treatment of type 2 diabetes...
December 21, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27993221/exendin-4-a-glucagon-like-peptide-1-analogue-accelerates-diabetic-wound-healing
#17
Jun-Neng Roan, Han-Ni Cheng, Chao-Chung Young, Chi-Ju Lee, Ming-Long Yeh, Chwan-Yau Luo, Yau-Sheng Tsai, Chen-Fuh Lam
BACKGROUND: Diabetes disregulates inflammatory responses and impairs vascular function in wounds. Glucagon-like peptide-1 receptor (Glp-1R) agonists are hypoglycemic agents with pleiotropic vascular protective and anti-inflammatory effects. The therapeutic potential of a Glp-1 analogue in a diabetic rat model of excisional wound injury was investigated. MATERIALS AND METHODS: Excisional wounds were created on the dorsum of streptozotocin-induced diabetic rats, which received placebo or Glp-1 analogue exendin-4 (Ex4; 0...
February 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/27992511/liraglutide-reduces-both-atherosclerosis-and-kidney-inflammation-in-moderately-uremic-ldlr-mice
#18
Line S Bisgaard, Markus H Bosteen, Lisbeth N Fink, Charlotte M Sørensen, Alexander Rosendahl, Christina K Mogensen, Salka E Rasmussen, Bidda Rolin, Lars B Nielsen, Tanja X Pedersen
Chronic kidney disease (CKD) leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis and atherosclerosis in uremic settings, insight into new treatment options with effects on both parameters is warranted. The GLP-1 analogue liraglutide improves glucose homeostasis, and is approved for treatment of type 2 diabetes...
2016: PloS One
https://www.readbyqxmd.com/read/27986341/incretin-related-drugs-and-cardiovascular-events-a-comparison-of-glp-1-analogue-and-dpp-4-inhibitor
#19
EDITORIAL
Yukihito Higashi
No abstract text is available yet for this article.
March 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/27941938/effects-of-exendin-4-on-human-adipose-tissue-inflammation-and-ecm-remodelling
#20
E Pastel, S Joshi, B Knight, N Liversedge, R Ward, K Kos
BACKGROUND/OBJECTIVES: Subjects with type-2 diabetes are typically obese with dysfunctional adipose tissue (AT). Glucagon-like peptide-1 (GLP-1) analogues are routinely used to improve glycaemia. Although, they also aid weight loss that improves AT function, their direct effect on AT function is unclear. To explore GLP-1 analogues' influence on human AT's cytokine and extracellular matrix (ECM) regulation, we therefore obtained and treated omental (OMAT) and subcutaneous (SCAT) AT samples with Exendin-4, an agonist of the GLP-1 receptor (GLP-1R)...
December 12, 2016: Nutrition & Diabetes
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