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GLP-1 diabetes obesity

Eisuke Kato
Plant materials have been widely studied for their preventive and therapeutic effects for type 2 diabetes mellitus (T2DM) and obesity. The effect of a plant material arises from its constituents, and the study of these bioactive compounds is important to achieve a deeper understanding of its effect at the molecular level. In particular, the study of the effects of such bioactive compounds on various biological processes, from digestion to cellular responses, is required to fully understand the overall effects of plant materials in these health contexts...
February 17, 2019: Bioscience, Biotechnology, and Biochemistry
Georgios A Christou, Niki Katsiki, John Blundell, Gema Fruhbeck, Dimitrios N Kiortsis
Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a long elimination half-life, allowing subcutaneous (sc) administration once per week. Both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) recently approved once-weekly sc semaglutide for the treatment of type 2 diabetes mellitus (T2DM). The weight loss efficacy of once-weekly sc semaglutide appears to be superior compared with the other once-weekly GLP-1 RAs in patients with T2DM. Semaglutide was recently evaluated as an antiobesity drug in a phase II dose-finding trial, which demonstrated superior weight loss efficacy of once daily sc semaglutide compared with both placebo and once daily 3...
February 15, 2019: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Vishal J Patel, Amit A Joharapurkar, Samadhan G Kshirsagar, Brijesh K Sutariya, Maulik S Patel, Rajesh H Bahekar, Mukul R Jain
BACKGROUND: Balanced coagonists of glucagon-like peptide-1 (GLP-1) and glucagon receptors are emerging therapies for the treatment of obesity and diabetes. Such coagonists also regulate lipid metabolism, independent of their body weight lowering effects. Many actions of the coagonists are partly mediated by fibroblast growth factor 21 (FGF21) signaling, with the major exception of bile homeostasis. Since thyroid hormone is an important regulator of bile homeostasis, we studied the involvement of thyroid hormone in coagonist-induced changes in lipid and bile metabolism...
February 11, 2019: Current Molecular Pharmacology
Malin Nilsson, Kira Bang Bové, Elena Suhrs, Thomas Hermann, Sten Madsbad, Jens Juul Holst, Eva Prescott, Mette Zander
Objective: Glucagon-like-peptide-1 (GLP-1) receptor analogues have been shown to reduce cardiovascular events in patients with type 2 diabetes. However, the mechanism behind is still unknown. The aim of the study was to investigate the effect of intact GLP-1 (7-36) on coronary microcirculation in overweight adults. Design and methods: A double-blinded randomized cross-over study was performed, with 12 overweight participants. Effects of intact GLP-1 (7-36) infusion were compared with a saline infusion on separate days...
March 2019: IJC Heart & Vasculature
Y L He, W Haynes, C D Meyers, A Amer, Y Zhang, P Chen, A E Mendonza, S Ma, W Chutkow, E Bachman
BACKGROUND: There is an unmet need for a safer and more effective treatment for obesity. This study assessed the effects of licogliflozin, a dual inhibitor of sodium-glucose co-transporter (SGLT) 1/2, on body weight, metabolic parameters and incretin hormones in patients with T2DM and/or obesity. METHODS: Patients with obesity (BMI 35-50kg/m2 ) were enrolled into a 12-week study (N=88; licogliflozin 150 mg q.d.). Patients with type-2 diabetes-mellitus (T2DM) were enrolled into a second, two-part study, comprising a single-dose cross-over (N=12; 2...
February 5, 2019: Diabetes, Obesity & Metabolism
J Arturo Prada-Oliveira, Alonso Camacho-Ramírez, Jesús Salas-Alvarez, Francisco Javier Campos-Martínez, Alfonso M Lechuga-Sancho, David Almorza-Gomar, Manuel Blandino-Rosano, Gonzalo M Pérez-Arana
OBJECTIVE: The aim of this study was to clarify the role of the middle gut in the entero-pancreatic axis modification that leads to glucose improvement in the Goto-Kakizaki (GK) rat as a non-obese T2DM model. BACKGROUND: Bariatric surgery is considered an assured solution for type 2 Diabetes (T2DM). Enterohormones such as ghrelin, gastric inhibitory polypeptide and mainly glucagon-like peptide-1 (GLP-1) were recognized as key players in the physiophathological mechanisms associated with entero-pancreatic axis regulation and glucose tolerance improvement...
February 2, 2019: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Shun He, Florian Kahles, Sara Rattik, Manfred Nairz, Cameron S McAlpine, Atsushi Anzai, Daniel Selgrade, Ashley M Fenn, Christopher T Chan, John E Mindur, Colin Valet, Wolfram C Poller, Lennard Halle, Noemi Rotllan, Yoshiko Iwamoto, Gregory R Wojtkiewicz, Ralph Weissleder, Peter Libby, Carlos Fernández-Hernando, Daniel J Drucker, Matthias Nahrendorf, Filip K Swirski
The biochemical response to food intake must be precisely regulated. Because ingested sugars and fats can feed into many anabolic and catabolic pathways1 , how our bodies handle nutrients depends on strategically positioned metabolic sensors that link the intrinsic nutritional value of a meal with intermediary metabolism. Here we describe a subset of immune cells-integrin β7+ natural gut intraepithelial T lymphocytes (natural IELs)-that is dispersed throughout the enterocyte layer of the small intestine and that modulates systemic metabolism...
January 30, 2019: Nature
Po-Kai Huang, Shian-Ren Lin, Jirawat Riyaphan, Yaw-Syan Fu, Ching-Feng Weng
Serine protease dipeptidyl peptidase 4 (DPP-4) is involved in self/non-self-recognition and insulin sensitivity. DPP-4 inhibitors are conventional choices for diabetic treatment; however, side effects such as headache, bronchus infection, and nasopharyngitis might affect the daily lives of diabetic patients. Notably, natural compounds are believed to have a similar efficacy with lower adverse effects. This study aimed to validate the DPP-4 inhibitory activity of clerodane diterpene 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) from Polyalthia longifolia , rutin, quercetin, and berberine, previously selected through molecular docking...
January 27, 2019: International Journal of Molecular Sciences
Natasha C Bergmann, Asger Lund, Lærke S Gasbjerg, Emma C E Meessen, Maria M Andersen, Sigrid Bergmann, Bolette Hartmann, Jens J Holst, Lene Jessen, Mikkel B Christensen, Tina Vilsbøll, Filip K Knop
AIMS/HYPOTHESIS: Glucagon-like peptide 1 (GLP-1) reduces appetite and energy intake in humans, whereas the other incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), seems to have no effect on eating behaviour. Interestingly, studies in rodents have shown that concomitant activation of GIP and GLP-1 receptors may potentiate the satiety-promoting effect of GLP-1, and a novel dual GLP-1/GIP receptor agonist was recently shown to trigger greater weight losses compared with a GLP-1 receptor agonist in individuals with type 2 diabetes...
January 25, 2019: Diabetologia
Hyeonhui Kim, Sungsoon Fang
Though bile acids have been well known as digestive juice, recent studies have demonstrated that bile acids bind to their endogenous receptors, including Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1; TGR5) and serve as hormone to control various biological processes, including cholesterol/bile acid metabolism, glucose/lipid metabolism, immune responses, and energy metabolism. Deficiency of those bile acid receptors has been reported to induce diverse metabolic syndromes such as obesity, hyperlipidemia, hyperglycemia, and insulin resistance...
December 2018: Laboratory Animal Research
F Samuel van Nierop, C de Jonge, W Kulik, Nicole Bouvy, Frank G Schaap, Steven W Olde Damink, Sander Rensen, Johannes A Romijn, Jan Willem M Greve, Maarten R Soeters
BACKGROUND AND AIMS: Placement of the duodenal-jejunal bypass liner (DJBL) leads to rapid weight loss and restoration of insulin sensitivity in a similar fashion to bariatric surgery. Increased systemic bile acid levels are candidate effectors for these effects through postprandial activation of their receptors TGR5 and FXR. We aimed to quantify postprandial bile acid, GLP-1 and FGF19 responses and assess their temporal relation to the weight loss and metabolic and hormonal changes seen after DJBL placement...
January 15, 2019: Metabolism: Clinical and Experimental
Marta Klementova, Lenka Thieme, Martin Haluzik, Renata Pavlovicova, Martin Hill, Terezie Pelikanova, Hana Kahleova
Gastrointestinal hormones are involved in regulation of glucose metabolism and satiety. We tested the acute effect of meal composition on these hormones in three population groups. A randomized crossover design was used to examine the effects of two energy- and macronutrient-matched meals: a processed-meat and cheese (M-meal) and a vegan meal with tofu (V-meal) on gastrointestinal hormones, and satiety in men with type 2 diabetes (T2D, n = 20), obese men (O, n = 20), and healthy men (H, n = 20). Plasma concentrations of glucagon-like peptide -1 (GLP-1), amylin, and peptide YY (PYY) were determined at 0, 30, 60, 120 and 180 min...
January 12, 2019: Nutrients
Claudia Guida, Sam D Stephen, Michael Watson, Niall Dempster, Pierre Larraufie, Thomas Marjot, Tamsin Cargill, Lisa Rickers, Michael Pavlides, Jeremy Tomlinson, Jeremy F L Cobbold, Chun-Mei Zhao, Duan Chen, Fiona Gribble, Frank Reimann, Richard Gillies, Bruno Sgromo, Patrik Rorsman, John D Ryan, Reshma D Ramracheya
BACKGROUND: Bariatric surgery leads to early and long-lasting remission of type 2 diabetes (T2D). However, the mechanisms behind this phenomenon remain unclear. Among several factors, gut hormones are thought to be crucial mediators of this effect. Unlike GLP-1, the role of the hormone peptide tyrosine tyrosine (PYY) in bariatric surgery in humans has been limited to appetite regulation and its impact on pancreatic islet secretory function and glucose metabolism remains under-studied...
January 11, 2019: EBioMedicine
Ryota Usui, Daisuke Yabe, Yutaka Seino
Unimolecular peptide-based dual agonists against glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) have been gaining much attention recently as novel anti-diabetic agents that can potentially control glycaemia and bodyweight. While glucagon-like Peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) both enhance insulin secretion and subsequently ameliorate postprandial glucose excursion, most research has focused on GLP-1R as a therapeutic target for type 2 diabetes...
January 13, 2019: Journal of Diabetes Investigation
Meena Jain, Glenn Carlson, William Cook, Linda Morrow, Marcella Petrone, Nicholas E White, Tao Wang, Jacqueline Naylor, Philip Ambery, Charles Lee, Boaz Hirshberg
AIMS/HYPOTHESIS: Cardiovascular disease is the leading cause of morbidity and mortality in people with type 2 diabetes. MEDI4166 is a proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody and glucagon-like peptide-1 (GLP-1) analogue fusion molecule designed to treat patients with type 2 diabetes who are at risk for cardiovascular disease. In this completed, first-in-human study, we evaluated the safety and efficacy of single or multiple doses of MEDI4166 in participants with type 2 diabetes...
December 28, 2018: Diabetologia
Meera Shah, Marcello C Laurenti, Chiara Dalla Man, Jing Ma, Claudio Cobelli, Robert A Rizza, Adrian Vella
Glucagon-Like Peptide-1 (GLP-1) is an insulin secretagogue which is elevated after Roux-en-Y Gastric Bypass (RYGB). However, its contribution to glucose metabolism after RYGB remains uncertain. AIMS: We tested the hypothesis that GLP-1 lowers postprandial glucose concentrations and improves β-cell function after RYGB. MATERIALS AND METHODS: To address these questions we used a labeled mixed meal to assess glucose metabolism and islet function in 12 obese subjects with type 2 diabetes studied before and four weeks after RYGB...
December 23, 2018: Metabolism: Clinical and Experimental
Carla Torre, José Guerreiro, Patrícia Longo, João Filipe Raposo, Hubert Leufkens, Ana Paula Martins
AIMS: To assess baseline and change after 26-weeks in health-related quality of life (HRQoL) among adults with type 2 diabetes mellitus (T2DM) initiating one of the new glucose lowering drugs (GLD) in daily practice. METHODS: Inception cohort of patients who initiated one of dipeptidyl peptidase 4 inhibitors (DPP-4), glucagon-like peptide-1 analogues (GLP-1) or sodium-glucose cotransporter inhibitors (SGLT2) drugs. A baseline questionnaire collected socio-demographic and self-reported clinical data...
December 17, 2018: Primary Care Diabetes
Noe Quesada-Vázquez
Liraglutide is a long-acting glucagon-like peptide-1 (GLP-1) analog. GLP-1 analogues are used as a second option treatment for type 2 diabetes and weight management in obese patients. Data in the literature suggests an association between GLP-1 agonist use and acute pancreatitis (AP). Furthermore, it has been suggested that acute pancreatitis is a potential complication of liraglutide therapy and liraglutide should be used cautiously in patients at risk of pancreatitis. This case reported herein was a 44-year-old female diagnosed with acute pancreatitis based on 2 of 3 criteria when she presented to the Emergency Department with epigastric pain, which radiated to her back...
December 18, 2018: Revista Española de Enfermedades Digestivas
Sofia S Pereira, Marta Guimarães, Rui Almeida, Ana M Pereira, Carolina B Lobato, Bolette Hartmann, Linda Hilsted, Jens J Holst, Mário Nora, Mariana P Monteiro
BACKGROUND/OBJECTIVE: Biliopancreatic diversion with duodenal switch (BPD-DS) is the most effective bariatric intervention to treat morbid obesity and related disorders. Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a new bariatric procedure devised with the purpose of simplifying the complexity of the BPD-DS technique while maintaining its efficacy. However, whether BPD-DS and SADI-S result in similar fasting and post-prandial hormone profiles has not yet been studied...
December 11, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Joseph Zhou, Anil Poudel, Prashanth Chandramani-Shivalingappa, Biao Xu, Ryan Welchko, Lixin Li
PURPOSE: Glucagon like peptide-1 (GLP-1) is produced to induce postprandial insulin secretion. Liraglutide, a full agonist of the GLP-1 receptor, has a protective effect on weight gain in obese subjects. Brown adipose tissue plays a major role in the control of energy balance and is known to be involved in the weight loss regulated by liraglutide. The putative anti-obesity properties of liraglutide and the cell signaling pathways involved were examined. METHODS: Four groups of C57/BL6 mice fed with chow or HFHS diet were injected with either liraglutide or vehicle for four weeks...
December 9, 2018: Endocrine
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