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https://www.readbyqxmd.com/read/29242349/efficacy-and-safety-of-itca-650-a-novel-drug-device-glp-1-receptor-agonist-in-type-2-diabetes-uncontrolled-with-oral-antidiabetes-drugs-the-freedom-1-trial
#1
Julio Rosenstock, John B Buse, Rehan Azeem, Prakash Prabhakar, Lise Kjems, Holly Huang, Michelle A Baron
OBJECTIVE: ITCA 650 (exenatide in osmotic mini-pump) continuously delivers exenatide subcutaneously for 3-6 months. Two doses of ITCA 650 were compared with placebo in patients with uncontrolled type 2 diabetes. RESEARCH DESIGN AND METHODS: This 39-week, phase 3, double-blind, placebo-controlled trial randomized 460 patients aged 18-80 years with glycated hemoglobin (HbA1c) 7.5-10% [58-86 mmol/mol] 1:1:1 to placebo, ITCA 650 40 μg/day, or ITCA 650 60 μg/day. Primary end point was change in HbA1c at 39 weeks...
December 14, 2017: Diabetes Care
https://www.readbyqxmd.com/read/29242286/hop-1-presenilin-deficiency-causes-a-late-onset-notch-signaling-phenotype-that-affects-adult-germline-function-in-c-elegans
#2
Ipsita Agarwal, Cassandra Farnow, Joshua Jiang, Kyung-Sik Kim, Donna E Leet, Ruth Z Solomon, Valerie A Hale, Caroline Goutte
Functionally redundant genes present a puzzle as to their evolutionary preservation, and offer an interesting opportunity for molecular specialization. In Caenorhabditis elegans, either one of two presenilin genes (sel-12 or hop-1) facilitate Notch activation, providing the catalytic subunit for the gamma secretase proteolytic enzyme complex.  For all known Notch signaling events, sel-12 can mediate Notch activation, so the conservation of hop-1 remains a mystery. Here, we uncover a novel "late-onset" germline Notch phenotype in which HOP-1-deficient worms fail to maintain proliferating germline stem cells during adulthood...
December 14, 2017: Genetics
https://www.readbyqxmd.com/read/29239601/preparation-and-pharmaceutical-characterizations-of-lipidated-dimeric-xenopus-glucagon-like-peptide-1-conjugates
#3
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/29238721/macrovascular-complications-in-patients-with-diabetes-and-prediabetes
#4
REVIEW
Dou Huang, Marwan Refaat, Kamel Mohammedi, Amin Jayyousi, Jassim Al Suwaidi, Charbel Abi Khalil
Diabetes is a significant health problem worldwide, and its association with cardiovascular disease (CVD) was reported in several studies. Hyperglycemia and insulin resistance seen in diabetes and prediabetes lead to an increase in reactive oxygen species, which triggers intracellular molecular signaling. The resulting prothrombotic state and increase in inflammatory mediators expedite atherosclerotic changes and the development of macrovascular complications. Individuals with diabetes or prediabetes have a higher risk of developing myocardial infarction, stroke, and peripheral artery disease...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29236983/cardioprotective-anti-hyperglycaemic-medications-a-review-of-clinical-trials
#5
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
#6
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/29235507/blood-brain-glucose-transfer-in-alzheimer-s-disease-effect-of-glp-1-analog-treatment
#7
Michael Gejl, Birgitte Brock, Lærke Egefjord, Kim Vang, Jørgen Rungby, Albert Gjedde
There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral metabolic rate for glucose (CMRglc) in AD, and GLP-1 may serve to raise transporter numbers. We hypothesized that the GLP-1 analog liraglutide would prevent the decline of CMRglc in AD by raising blood-brain glucose transfer, depending on the duration of disease...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29235009/duodenal-exclusion-but-not-sleeve-gastrectomy-preserves-insulin-secretion-making-it-the-more-effective-metabolic-procedure
#8
Claudia Laessle, Gergana Nenova, Goran Marjanovic, Gabriel Seifert, Lampros Kousoulas, Bernd Jaenigen, Stefan Fichtner-Feigl, Jodok Matthias Fink
INTRODUCTION: There is an ongoing debate on which procedure provides the best treatment for type 2 diabetes. Furthermore, the pathomechanisms of diabetes improvement of partly anatomically differing operations is not fully understood. METHODS: A loop duodenojejunostomy (DJOS) with exclusion of one third of intestinal length, a sleeve gastrectomy (SG), or a combination of DJOS + SG was performed in 8-week-old male ZDF rats. One, three, and six months after surgery, an oral glucose tolerance test and measurements of GLP-1, GIP, insulin, and bile acids were conducted...
December 12, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/29233907/glucagon-like-peptide-1-acutely-affects-renal-blood-flow-and-urinary-flow-rate-in-spontaneously-hypertensive-rats-despite-significantly-reduced-renal-expression-of-glp-1-receptors
#9
Jonas Ronn, Elisa P Jensen, Nicolai J Wewer Albrechtsen, Jens Juul Holst, Charlotte M Sorensen
Glucagon-like peptide-1 (GLP-1) is an incretin hormone increasing postprandial insulin release. GLP-1 also induces diuresis and natriuresis in humans and rodents. The GLP-1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP-1 treatment leads to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect of acute intrarenal infusion of GLP-1...
December 2017: Physiological Reports
https://www.readbyqxmd.com/read/29231147/neuroendocrine-and-metabolic-disorders-in-bulimia-nervosa
#10
Walter Milano, Anna Capasso
BACKGROUND AND OBJECTIVE: Bulimia nervosa, is an eating disorder characterized by excessive influence of weight and body shape on the levels of self-esteem, with pervasive feelings of failure and inadequacy. The eating is characterized by the presence of episodes of uncontrolled eating (Binge), during which the person ingests mass wide variety of foods and the feeling of not being able to stop eating. This review focuses on the metabolic and hormonal alterations in the in bulimia nervosa...
December 11, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29229616/glutamine-elicited-secretion-of-glucagon-like-peptide-1-glp-1-is-governed-by-an-activated-glutamate-dehydrogenase
#11
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
#12
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
#13
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/29226685/size-effect-on-lipid-nanocapsules-mediated-glp-1-secretion-from-enteroendocrine-l-cells
#14
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
#15
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/29226617/activation-of-glucagon-like-peptide-1-receptors-in-the-nucleus-accumbens-attenuates-cocaine-seeking-in-rats
#16
Nicole S Hernandez, Bernadette O'Donovan, Pavel I Ortinski, Heath D Schmidt
Recent evidence indicates that activation of glucagon-like peptide-1 (GLP-1) receptors reduces cocaine-mediated behaviors and cocaine-evoked dopamine release in the nucleus accumbens (NAc). However, no studies have examined the role of NAc GLP-1 receptors in the reinstatement of cocaine-seeking behavior, an animal model of relapse. Here, we show that systemic infusion of a behaviorally relevant dose of the GLP-1 receptor agonist exendin-4 penetrated the brain and localized with neurons and astrocytes in the NAc...
December 11, 2017: Addiction Biology
https://www.readbyqxmd.com/read/29225158/exendin-4-partly-ameliorates-of-hyperglycemia-mediated-tissue-damage-in-lungs-of-streptozotocin-induced-diabetic-mice
#17
Fusun Oztay, Serap Sancar Bas, Selda Gezginci-Oktayoglu, Merve Ercin, Sehnaz Bolkent
Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion, and plays anti-inflammatory role in atherosclerosis, and has surfactant-releasing effects in lungs. GLP-1 analogues are used in diabetes therapy. This is the first study to investigate the effects of exendin-4, a GLP-1 receptor agonist, on lung injury in diabetic mice. BALB/c male mice were divided into four groups. The first group was given only citrate buffer, the second group was given only exendin-4, the third group was given only streptozotocin (STZ), and the fourth group was given both exendin-4 and STZ...
December 7, 2017: Peptides
https://www.readbyqxmd.com/read/29224011/glp-1-and-ghrelin-attenuate-high-glucose-high-lipid-induced-apoptosis-and-senescence-of-human-microvascular-endothelial-cells
#18
Pengzhi Liao, Dan Yang, Duan Liu, Yuehong Zheng
BACKGROUND/AIMS: GLP-1 and ghrelin are common appetite-regulating hormones. Both have multiple functions beyond metabolic regulation. However, the effects of GLP-1 and ghrelin on endothelial biology are not fully understood. Here, we investigate the roles of GLP-1 and ghrelin in microvascular endothelial apoptosis and senescence. METHODS: Human microvascular endothelial cells (HMECs) were exposed to high glucose/high lipid (HG/HL) conditions and treated with GLP-1 or ghrelin...
December 7, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29223528/glp-1-receptor-agonists-downregulate-aberrant-gnt-iii-expression-in-alzheimer-s-disease-models-through-the-akt-gsk-3%C3%AE-%C3%AE-catenin-signaling
#19
Ying Wang, Song Chen, Zheng Xu, Suting Chen, Wenbing Yao, Xiangdong Gao
Alterations of glycoprotein glycans contribute to a wide variety of diseases. Bisecting N-acetylglucosamine (GlcNAc) levels increased in the cerebrospinal fluid of most Alzheimer's disease (AD) patients, and the mRNA levels of N-acetylglucosaminyltransferase III (GnT-III), a glycosyltransferase responsible for synthesizing a bisecting GlcNAc residue, were found highly expressed in the brains of AD patients. In our previous studies, glucagon-like peptide-1 (GLP-1) and its mimetics showed neuroprotective effects...
December 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29221794/glp-1-action-in-the-mouse-bed-nucleus-of-the-stria-terminalis
#20
Diana L Williams, Nicole A Lilly, Ian J Edwards, Pallas Yao, James E Richards, Stefan Trapp
Glucagon-like peptide-1 (GLP-1) injected into the brain reduces food intake. Similarly, activation of preproglucagon (PPG) cells in the hindbrain which synthesize GLP-1, reduces food intake. However, it is far from clear whether this happens because of satiety, nausea, reduced reward, or even stress. Here we explore the role of the bed nucleus of the stria terminalis (BNST), an area involved in feeding control as well as stress responses, in GLP-1 responses. Using cre-expressing mice we visualized projections of NTS PPG neurons and GLP-1R-expressing BNST cells with AAV-driven Channelrhodopsin-YFP expression...
December 5, 2017: Neuropharmacology
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