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obesity AND GLP-1

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https://www.readbyqxmd.com/read/29330461/comparing-olive-oil-and-c4-dietary-oil-a-prodrug-for-the-gpr119-agonist-2-oleoyl-glycerol-less-energy-intake-of-the-latter-is-needed-to-stimulate-incretin-hormone-secretion-in-overweight-subjects-with-type-2-diabetes
#1
Mette Johannsen Mandøe, Katrine Bagge Hansen, Johanne Agerlin Windeløv, Filip Krag Knop, Jens Frederik Rehfeld, Mette Marie Rosenkilde, Jens Juul Holst, Harald Severin Hansen
BACKGROUND/OBJECTIVE: After digestion, dietary triacylglycerol stimulates incretin release in humans, mainly through generation of 2-monoacylglycerol, an agonist for the intestinal G protein-coupled receptor 119 (GPR119). Enhanced incretin release may have beneficial metabolic effects. However, dietary fat may promote weight gain and should therefore be restricted in obesity. We designed C4-dietary oil (1,3-di-butyryl-2-oleoyl glycerol) as a 2-oleoyl glycerol (2-OG)-generating fat type, which would stimulate incretin release to the same extent while providing less calories than equimolar amounts of common triglycerides, e...
January 12, 2018: Nutrition & Diabetes
https://www.readbyqxmd.com/read/29330364/polypharmacy-through-phage-display-selection-of-glucagon-and-glp-1-receptor-co-agonists-from-a-phage-displayed-peptide-library
#2
Anna Demartis, Armin Lahm, Licia Tomei, Elisa Beghetto, Valentina Di Biasio, Federica Orvieto, Francesco Frattolillo, Paul E Carrington, Sheena Mumick, Brian Hawes, Elisabetta Bianchi, Anandan Palani, Antonello Pessi
A promising emerging area for the treatment of obesity and diabetes is combinatorial hormone therapy, where single-molecule peptides are rationally designed to integrate the complementary actions of multiple endogenous metabolically-related hormones. We describe here a proof-of-concept study on developing unimolecular polypharmacy agents through the use of selection methods based on phage-displayed peptide libraries (PDL). Co-agonists of the glucagon (GCG) and GLP-1 receptors were identified from a PDL sequentially selected on GCGR- and GLP1R-overexpressing cells...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29327400/a-vitamin-b12-conjugate-of-exendin-4-improves-glucose-tolerance-without-associated-nausea-or-hypophagia-in-rodents
#3
Elizabeth G Mietlicki-Baase, Claudia G Liberini, Jayme L Workinger, Ron L Bonaccorso, Tito Borner, David J Reiner, Kieran Koch-Laskowski, Lauren E McGrath, Rinzin Lhamo, Lauren M Stein, Bart C De Jonghe, George G Holz, Christian L Roth, Robert P Doyle, Matthew R Hayes
AIMS: While pharmacological glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved for treating type 2 diabetes mellitus (T2DM) and obesity, a major side effect is nausea/malaise. We recently developed a conjugate of vitamin B12 bound to the GLP-1R agonist exendin-4 (Ex4), which displays enhanced proteolytic stability and retention of GLP-1R agonism. Here, we evaluate whether the conjugate (B12-Ex4) can improve glucose tolerance without producing anorexia and malaise. MATERIALS AND METHODS: We evaluated the effects of systemic B12-Ex4 and unconjugated Ex4 on food intake and body weight change, oral glucose tolerance, and nausea/malaise in male rats, and on intraperitoneal glucose tolerance in mice...
January 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29325849/coagonist-of-glp-1-and-glucagon-decreases-liver-inflammation-and-atherosclerosis-in-dyslipidemic-condition
#4
Vishal Patel, Amit Joharapurkar, Samadhan Kshirsagar, Brijesh Sutariya, Maulik Patel, Dhreerendra Pandey, Hiren Patel, Ramchandra Ranvir, Shekhar Kadam, Dipam Patel, Rajesh Bahekar, Mukul Jain
Dyslipidemia enhances progression of atherosclerosis. Coagonist of GLP-1 and glucagon are under clinical investigation for the treatment of obesity and diabetes. Earlier, we have observed that coagonist reduced circulating and hepatic lipids, independent of its anorexic effects. Here, we investigated the role of coagonist of GLP-1 and glucagon receptors in complications of diet-induced dyslipidemia in hamsters and humanized double transgenic mice. Hamsters fed on high fat high cholesterol diet were treated for 8 weeks with coagonist of GLP-1 and glucagon receptors (75 and 150 μg/kg)...
January 8, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29322485/effects-of-ipragliflozin-on-postprandial-glucose-metabolism-and-gut-peptides-in-type-2-diabetes-a-pilot-study
#5
Hiroaki Ueno, Hiroko Nakazato, Emi Ebihara, Kenji Noma, Takahisa Kawano, Kazuhiro Nagamine, Hideyuki Sakoda, Masamitsu Nakazato
INTRODUCTION: Ipragliflozin is a novel antidiabetic drug that inhibits renal tubular sodium-glucose cotransporter-2 (SGLT2). The aim of this study was to evaluate the effects of ipragliflozin on glucose, insulin, glucagon, and gastrointestinal peptide responses to a meal tolerance test, as well as to investigate the glucose-lowering mechanisms of ipragliflozin. METHODS: Nine Japanese patients with obesity and type 2 diabetes mellitus were treated with ipragliflozin (50 mg/day) for 12 weeks...
January 10, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29317623/glp-1-release-and-vagal-afferent-activation-mediate-the-beneficial-metabolic-and-chronotherapeutic-effects-of-d-allulose
#6
Yusaku Iwasaki, Mio Sendo, Katsuya Dezaki, Tohru Hira, Takehiro Sato, Masanori Nakata, Chayon Goswami, Ryohei Aoki, Takeshi Arai, Parmila Kumari, Masaki Hayakawa, Chiaki Masuda, Takashi Okada, Hiroshi Hara, Daniel J Drucker, Yuichiro Yamada, Masaaki Tokuda, Toshihiko Yada
Overeating and arrhythmic feeding promote obesity and diabetes. Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective anti-obesity drugs but their use is limited by side effects. Here we show that oral administration of the non-calorie sweetener, rare sugar D-allulose (D-psicose), induces GLP-1 release, activates vagal afferent signaling, reduces food intake and promotes glucose tolerance in healthy and obese-diabetic animal models. Subchronic D-allulose administered at the light period (LP) onset ameliorates LP-specific hyperphagia, visceral obesity, and glucose intolerance...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29311617/scfas-strongly-stimulate-pyy-production-in-human-enteroendocrine-cells
#7
P Larraufie, C Martin-Gallausiaux, N Lapaque, J Dore, F M Gribble, F Reimann, H M Blottiere
Peptide-YY (PYY) and Glucagon-Like Peptide-1 (GLP-1) play important roles in the regulation of food intake and insulin secretion, and are of translational interest in the field of obesity and diabetes. PYY production is highest in enteroendocrine cells located in the distal intestine, mirroring the sites where high concentrations of short chain fatty acids (SCFAs) are produced by gut microbiota. We show here that propionate and butyrate strongly increased expression of PYY but not GCG in human cell line and intestinal primary culture models...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29310645/effects-of-6-month-treatment-with-the-glucagon-like-peptide-1-analogue-liraglutide-on-arterial-stiffness-left-ventricular-myocardial-deformation-and-oxidative-stress-in-subjects-with-newly-diagnosed-type-2-diabetes
#8
Vaia Lambadiari, George Pavlidis, Foteini Kousathana, Maria Varoudi, Dimitrios Vlastos, Eirini Maratou, Dimitrios Georgiou, Ioanna Andreadou, John Parissis, Helen Triantafyllidi, John Lekakis, Efstathios Iliodromitis, George Dimitriadis, Ignatios Ikonomidis
BACKGROUND: Incretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. We investigated the changes in arterial stiffness and left ventricular (LV) myocardial deformation after 6-month treatment with the GLP-1 analogue liraglutide in subjects with newly diagnosed T2DM. METHODS: We randomized 60 patients with newly diagnosed and treatment-naive T2DM to receive either liraglutide (n = 30) or metformin (n = 30) for 6 months...
January 8, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29275178/central-administration-of-coagonist-of-glp-1-and-glucagon-receptors-improves-dyslipidemia
#9
Vishal Patel, Amit Joharapurkar, Samadhan Kshirsagar, Brijesh Sutariya, Maulik Patel, Hiren Patel, Dheerendra Pandey, Dipam Patel, Rajesh Bahekar, Mukul Jain
Coagonists of Glucagon-like peptide-1 (GLP-1) and glucagon receptors are under clinical investigation for treatment of obesity associated with diabetes. In addition to their role in glucose homeostasis, GLP-1 and glucagon modulate lipid metabolism. In this study, we have investigated the role of central GLP-1 receptor (GLP-1R) and glucagon receptor (GCGR) activation in regulation of lipid metabolism in cholesterol-fed hamsters. Hamsters were treated with coagonist alone (0.3 μg) or in combination with either GLP-1R antagonist (0...
December 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29259802/the-effect-of-the-glp-1-analogue-exenatide-on-functional-connectivity-within-an-nts-based-network-in-women-with-and-without-obesity
#10
K Coveleskie, L A Kilpatrick, A Gupta, J Stains, L Connolly, J S Labus, C Sanmiguel, E A Mayer
Objective: The differential effect of GLP-1 agonist Exenatide on functional connectivity of the nucleus tractus solitaries (NTS), a key region associated with homeostasis, and on appetite-related behaviours was investigated in women with normal weight compared with women with obesity. Methods: Following an 8-h fast, 19 female subjects (11 lean, 8 obese) participated in a 2-d double blind crossover study. Subjects underwent functional magnetic resonance imaging at fast and 30-min post subcutaneous injection of 5 μg of Exenatide or placebo...
December 2017: Obesity Science & Practice
https://www.readbyqxmd.com/read/29245916/laminarin-counteracts-diet-induced-obesity-associated-with-glucagon-like-peptide-1-secretion
#11
Liusong Yang, Lina Wang, Canjun Zhu, Junguo Wu, Yexian Yuan, Lulu Yu, Yaqiong Xu, Jingren Xu, Tao Wang, Zhengrui Liao, Songbo Wang, Xiaotong Zhu, Ping Gao, Yongliang Zhang, Xiuqi Wang, Qingyan Jiang, Gang Shu
Laminarin, a type of β-glucan isolated from brown seaweeds, exhibits verity of physiological activities, which include immunology modulation and antitumor function. To investigate the effect of laminarin on energy homeostasis, mice were orally administrated with laminarin to test food intake, fat deposition, and glucose homeostasis. Chronically, laminarin treatment significantly decreases high-fat-diet-induced body weight gain and fat deposition and reduces blood glucose level and glucose tolerance. Acutely, laminarin enhances serum glucagon-like peptide-1 (GLP-1) content and the mRNA expression level of proglucagon and prohormone convertase 1 in ileum...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29216336/managing-diabetic-kidney-disease
#12
Sagen Zac-Varghese, Peter Winocour
Introduction: Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD). This review covers the pillars of care essential for the management of diabetic kidney disease (DKD) including (1) early diagnosis, (2) improved glycaemic control, (3) treatment of hypertension, (4) identification and treatment of associated metabolic bone disease and (5) identification and effective management of dyslipidaemia and additional cardiovascular risk factors. Sources of data: We searched PubMed for articles using search terms: diabetic nephropathy, diabetic kidney disease, diabetes and chronic kidney disease...
December 5, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/29194917/treatment-of-clozapine-associated-obesity-and-diabetes-with-exenatide-codex-in-adults-with-schizophrenia-a-randomised-controlled-trial
#13
Dan Siskind, Anthony W Russell, Clare Gamble, Karl Winckel, Karla Mayfield, Sam Hollingworth, Ingrid Hickman, Victor Siskind, Steve Kisely
Clozapine causes obesity and type-2 diabetes (T2DM). Glucagon-like-peptide-1 (GLP-1) agonists (e.g. exenatide) can counter clozapine-associated GLP-1 dysregulation in animals, and may be beneficial in people on clozapine. This randomised, controlled, open-label, pilot trial evaluated weekly exenatide for weight loss among clozapine-treated obese adults with schizophrenia, with or without T2DM. Twenty-eight outpatients were randomised to once-weekly extended-release sub-cutaneous exenatide or usual care for 24 weeks...
November 30, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29193738/cooperative-role-of-the-glp-1-receptor-and-%C3%AE-3-adrenergic-mediated-signaling-on-fat-mass-reduction-through-the-down-regulation-of-pka-akt-ampk-signaling-in-the-adipose-tissue-and-muscle-of-rats
#14
Juan Decara, Patricia Rivera, Sergio Arrabal, Antonio Vargas, Antonia Serrano, Francisco Javier Pavón, Carlos Dieguez, Rubén Nogueiras, Fernando Rodríguez de Fonseca, Juan Suárez
AIM: To explore the cooperation of GLP-1 receptor and β3-adrenergic receptor-mediated signaling in the control of fat mass/feeding behavior by studying the effects of a combined therapy composed of the GLP-1R agonist liraglutide and the β3-AR agonist CL316243. METHODS: The study included the analysis of key mechanisms regulating lipid/cholesterol metabolism, and thermogenesis in brown (BAT) and epididymal white (eWAT) adipose tissues, abdominal muscle and liver of male rats...
November 28, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29191090/alterations-in-circadian-and-meal-induced-gut-peptide-levels-in-lean-and-obese-rats
#15
Alexander A Moghadam, Timothy H Moran, Megan J Dailey
Alterations in gut hormone signaling are a likely contributing factor to the metabolic disturbances associated with overweight/obesity as they coordinate the timing of feeding behavior, absorption, and utilization of nutrients. These hormones are released in response to food intake, or follow a circadian or anticipatory pattern of secretion that is independent of nutrient stimulation. The aim of this study was to identify the degree to which high-fat diet-induced obesity would alter the daily rhythm of gut peptide plasma levels (glucagon-like peptide-1 [GLP-1], peptide YY [PYY], insulin or amylin [AMY]) or meal-induced levels in the middle of the light or dark cycle...
December 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29180139/combined-gastrin-releasing-peptide-29-and-glucagon-like-peptide-1-reduce-body-weight-more-than-each-individual-peptide-in-diet-induced-obese-male-rats
#16
Thaer R Mhalhal, Martha C Washington, Kayla D Newman, John C Heath, Ayman I Sayegh
To test the hypothesis that gastrin releasing peptide-29 (GRP-29) combined with glucagon like peptide-1 (7-36) (GLP-1 (7-36)) reduce body weight (BW) more than each of the peptides given individually, we infused the two peptides (0.5nmol/kg each) in the aorta of free feeding, diet-induced obese (DIO) male Sprague Dawley rats once daily for 25days and measured BW. We found that GRP-29 and GLP-1 reduce BW, GRP-29 reduced it more than GLP-1 and GRP-29+GLP-1 reduce BW more than each peptide given alone. This reduction was accompanied by decrease 24-hour food intake (normal rat chow), meal size (MS), duration of first meal and number of meals, and increase latency to the first meal, intermeal interval (IMI) and satiety ratio (IMI/MS, amount of food consumed per a unit of time)...
November 21, 2017: Neuropeptides
https://www.readbyqxmd.com/read/29169891/construction-of-a-novel-vaccine-by-conjugating-a-b-cell-epitope-of-dpp4-to-peptide-ia2-5-p2-1-to-significantly-control-type-1-diabetes-in-nod-mice
#17
Ya Li, Huimin Cao, Yiping Li, Zhixin Li, Xiaomin Wei, Rui Jiao, Peng Cheng, Xiaoran Liu, Yanjie Ma, Yun Xing, Jiali Tang, Min Wang, Taiming Li
Type 1 diabetes is a chronic organ-specific autoimmune disease in which selective destruction of insulin-producing β cells leads to impaired glucose metabolism and its attendant complications. IA2(5)P2-1, a potent immunogenic carrier which designed by our laboratory, can induce high titer specific antibodies when carry a B cell epitope, such as B cell epitopes of DPP4, xanthine oxidase, and Urate transporter protein. In this report, we describe a novel multi-epitope vaccine composing a peptide of DPP4, an anti-diabetic B epitope of Insulinoma antigen-2(IA-2) and a Th2 epitope (P2:IPALDSLTPANED) of P277 peptide in human heat shock protein 60 (HSP60)...
November 20, 2017: Vaccine
https://www.readbyqxmd.com/read/29167470/glucagon-like-peptide-1-mimetics-optimal-for-asian-type-2-diabetes-patients-with-and-without-overweight-obesity-meta-analysis-of-randomized-controlled-trials
#18
Fang Zhang, Lizhi Tang, Yuwei Zhang, Qingguo Lü, Nanwei Tong
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are desirable for diabetes, especially in patients with overweight/obesity. We aimed to determine whether GLP-1RAs exhibit different glucose-lowering efficacies between Asian type 2 diabetes (T2D) patients with and without overweight/obesity. Randomized controlled trials were searched in EMBASE, MEDLINE, CENTRAL, and ClinicalTrials.gov. Studies published in English with treatment duration ≥12 weeks and information on HbA1c changes were included. The studies were divided into normal body mass index (BMI) and overweight/obese groups according to baseline BMI...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29144968/a-synaptic-basis-for-glp-1-action-in-the-brain
#19
Sandrine Lefort, Matthias H Tschöp, Cristina García-Cáceres
Unraveling the brain control of metabolism may generate opportunities to discover novel precision medicines for obesity and diabetes. In this issue of Neuron, Liu et al. (2017) identify a novel glucagon-like peptide (GLP)-1 receptor-dependent signaling process that exerts anorexigenic action via the regulation of AMPA receptor subunit composition in the hypothalamus.
November 15, 2017: Neuron
https://www.readbyqxmd.com/read/29144805/dpp4-inhibitor-sitagliptin-as-a-potential-treatment-option-in-metformin-intolerant-obese-women-with-polycystic-ovary-syndrome-a-pilot-randomized-study
#20
Simona Ferjan, Andrej Janez, Mojca Jensterle
OBJECTIVE: Metformin has an established role in the management of polycystic ovary syndrome (PCOS). Some patients cannot tolerate it due to associated gastrointestinal adverse events. The present study evaluated DPP4 inhibitor sitagliptin as a potential treatment option in metformin intolerant PCOS. DESIGN: We conducted a 12-week prospective randomized open-label study with 30 obese metformin intolerant women with PCOS (aged 35.0±7.2 years, BMI 36.9±5.5 kg/m(2))...
November 16, 2017: Endocrine Practice
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