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obesity AND GLP-1

Gemma Pujadas, Daniel J Drucker
Regulatory peptides produced in islet and gut endocrine cells, including glucagon, GLP-1, GLP-2, and GIP exert actions with considerable metabolic importance and translational relevance. Although the clinical development of GLP-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4(DPP4) inhibitors has fostered research into how these hormones act on the normal and diseased heart, less is known about the actions of these peptides on blood vessels. Here we review the effects of these peptide hormones on normal blood vessels, and highlight their vascular actions in the setting of experimental and clinical vascular injury...
October 12, 2016: Endocrine Reviews
Pelle L Ishøy, Filip K Knop, Brian V Broberg, Nikolaj Bak, Ulrik B Andersen, Niklas R Jørgensen, Jens J Holst, Birte Y Glenthøj, Bjørn H Ebdrup
AIMS: Schizophrenia is associated with cardiovascular co-morbidity and a reduced life-expectancy of up to 20 years. Antipsychotics are dopamine D2 receptor antagonists and the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects like obesity and diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are registered for treatment of both obesity and type 2 diabetes. We investigated metabolic effects of the GLP-1RA, exenatide once-weekly, in non-diabetic, antipsychotic-treated, obese patients with schizophrenia...
September 26, 2016: Diabetes, Obesity & Metabolism
P Mensberg, S Nyby, P G Jørgensen, H Storgaard, M T Jensen, J Sivertsen, J J Holst, B Kiens, E A Richter, F K Knop, T Vilsbøll
AIMS: Exercise as well as glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment improves glycaemic control in patients with type 2 diabetes. We investigated the effects of exercise in combination with a GLP-1RA (liraglutide) or placebo for the treatment of type 2 diabetes. METHODS: Thirty-three overweight, dysregulated and sedentary patients with type 2 diabetes were randomly allocated to 16 weeks of exercise and liraglutide or exercise and placebo. Both groups had three supervised 60-minute training sessions per week including spinning and resistance training...
September 26, 2016: Diabetes, Obesity & Metabolism
Sang Ah Lee, Gwanpyo Koh, Suk Ju Cho, So Yeon Yoo, Sang Ouk Chin
BACKGROUND: Previous studies have reported that glypican-4 (GPC4) regulates insulin signaling by interacting with insulin receptor and through adipocyte differentiation. However, GPC4 has not been studied with regard to its effects on clinical factors in patients with type 2 diabetes mellitus (T2DM). We aimed to identify factors associated with GPC4 level in T2DM. METHODS: Between January 2010 and December 2013, we selected 152 subjects with T2DM and collected serum and plasma into tubes pretreated with aprotinin and dipeptidyl peptidase-4 inhibitor to preserve active gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1)...
September 2016: Endocrinology and Metabolism
Ulrich Rohde, Cecilie A Federspiel, Peter Vilmann, Ebbe Langholz, Steffen U Friis, Martin Krakauer, Jens F Rehfeld, Jens J Holst, Tina Vilsbøll, Filip K Knop
AIMS: The duodenal-jejunal bypass sleeve ((DJBS) or EndoBarrier Gastrointestinal Liner) induces weight loss in obese subjects and may improve glucose homeostasis in patients with type 2 diabetes (T2D). To explore the underlying mechanisms, we evaluated postprandial physiology including glucose metabolism, gut hormone secretion, gallbladder emptying, appetite and food intake in patients undergoing DJBS treatment. MATERIAL AND METHODS: Ten normal glucose tolerant (NGT) obese subjects and nine age, body weight and body mass index-matched metformin-treated T2D patients underwent a liquid mixed meal test and a subsequent ad libitum meal test before implantation with DJBS and one (1w) and 26 weeks (26w) after implantation...
October 3, 2016: Diabetes, Obesity & Metabolism
Herpreet Deol, Leoni Lekkakou, Ananth K Viswanath, Joseph M Pappachan
Diabesity-obesity resulting in diabetes-is a major health problem globally because of the obesity epidemic. Several anti-diabetic medications cause weight gain and may worsen obesity, and possibly diabeisty. Two recent small retrospective cohort studies showed weight loss and diabetes improvement with combination of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co-transporter type-2 (SGLT-2) inhibitors in obese subjects. We assessed the effect of combination therapy with GLP-1 agonists and SGLT-2 inhibitors in the management of diabesity in a retrospective study at the Wolverhampton Diabetes Centre...
September 30, 2016: Endocrine
Hitesh Soni
Diabesity is a new term for obesity-dependent diabetes, which is also associated with cardiovascular and other comorbidities with rising epidemic. Traditional treatments (sulfonylureas and thiazolidinediones) of diabetes are associated with weight gain, except metformin. Newer agents such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and Sodium glucose co-transporter 2 inhibitors (SGLT2i) are causing a modest weight reduction, whereas dipeptidyl peptidase-4 inhibitors (DPP-4i) are weight neutral...
October 2016: Medical Hypotheses
Ioannis Christakis, Rebecca Scott, James Minnion, Joyceline Cuenco, Tricia Tan, Fausto Palazzo, Stephen Bloom
PURPOSE/AIM OF THE STUDY: The pharmacokinetic (PK) parameters in animal models can help optimize novel candidate drugs prior to human trials. However, due to the complexity of pharmacokinetic experiments, their use is limited in academia. We present a novel surgical rat model for investigation of pharmacokinetic parameters and its use in an anti-obesity drug development program. MATERIALS AND METHODS: The model uses anesthetized male Wistar rats, a jugular, a femoral catheter, and an insulin pump for peptide infusion...
September 30, 2016: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
Sara Baldassano, Antonella Amato, Flavia Mulè
Glucagon like peptide-2 (GLP-2) is a gastrointestinal hormone released from enteroendocrine L-type cells together with glucagon like peptide-1 in response to dietary nutrients. GLP-2 acts through a specific receptor, the GLP-2 receptor, mainly located in the gut and in the brain. Classically, GLP-2 is considered a trophic hormone involved in the maintenance of intestinal epithelial morphology and function. This role has been targeted for therapies promoting repair and adaptive growth of the intestinal mucosa...
September 21, 2016: Peptides
F Samuel van Nierop, Matthijs J Scheltema, Hannah M Eggink, Thijs W Pols, David P Sonne, Filip K Knop, Maarten R Soeters
The bile acid receptor TGR5 (also known as GPBAR1) is a promising target for the development of pharmacological interventions in metabolic diseases, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. TGR5 is expressed in many metabolically active tissues, but complex enterohepatic bile acid cycling limits the exposure of some of these tissues to the receptor ligand. Profound interspecies differences in the biology of bile acids and their receptors in different cells and tissues exist. Data from preclinical studies show promising effects of targeting TGR5 on outcomes such as weight loss, glucose metabolism, energy expenditure, and suppression of inflammation...
September 14, 2016: Lancet Diabetes & Endocrinology
Kazunari Kamiko, Kazutaka Aoki, Hiroshi Kamiyama, Masataka Taguri, Yasuo Terauchi
BACKGROUND: A fast eating speed is reportedly associated with obesity, fatty liver, and metabolic syndrome. As a comparison of postprandial glucose levels after eating quickly or slowly has not been previously reported for Japanese patients with type 2 diabetes, we evaluated the impact of the fast or slow ingestion of an enteral formula (liquid meal) on glucose metabolism. METHODS: Ten Japanese patients with type 2 diabetes who had been hospitalized at our hospital were enrolled...
October 2016: Journal of Clinical Medicine Research
Chris de Graaf, Dan Donnelly, Denise Wootten, Jesper Lau, Patrick M Sexton, Laurence J Miller, Jung-Mo Ahn, Jiayu Liao, Madeleine M Fletcher, Dehua Yang, Alastair J H Brown, Caihong Zhou, Jiejie Deng, Ming-Wei Wang
The glucagon-like peptide (GLP)-1 receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone secreted from three major tissues in humans, enteroendocrine L cells in the distal intestine, α cells in the pancreas, and the central nervous system, which exerts important actions useful in the management of type 2 diabetes mellitus and obesity, including glucose homeostasis and regulation of gastric motility and food intake. Peptidic analogs of GLP-1 have been successfully developed with enhanced bioavailability and pharmacological activity...
October 2016: Pharmacological Reviews
Joost Overduin, Tinh-Hai Collet, Nenad Medic, Elana Henning, Julia M Keogh, Faye Forsyth, Cheryl Stephenson, Marja W Kanning, Rianne M A J Ruijschop, I Sadaf Farooqi, Agatha A van der Klaauw
There is considerable interest in the effect of foods containing high intensity sweeteners on satiation. However, less is known about low-calorie bulk sweeteners such as erythritol. In this randomized three-way crossover study, we studied 10 lean and 10 obese volunteers who consumed three test meals on separate occasions: (a) control sucrose meal; (b) isovolumic meal with partial replacement of sucrose by erythritol; (c) isocaloric meal which contained more erythritol but equivalent calories to the control meal...
September 9, 2016: Appetite
Thomas U Greiner, Fredrik Bäckhed
BACKGROUND: The gut microbiota is associated with several of metabolic diseases, including obesity and type 2 diabetes and affects host physiology through distinct mechanisms. The microbiota produces a vast array of metabolites that signal to host cells in the intestine as well as in more distal organs. SCOPE OF REVIEW: Enteroendocrine cells acts as 'chemo sensors' of the intestinal milieu by expressing a large number of receptors, which respond to different metabolites and nutrients, and signal to host by a wide variety of hormones...
September 2016: Molecular Metabolism
Lydia Lynch, Andrew E Hogan, Danielle Duquette, Chantel Lester, Alexander Banks, Katherine LeClair, David E Cohen, Abhisek Ghosh, Bing Lu, Michelle Corrigan, Darko Stevanovic, Eleftheria Maratos-Flier, Daniel J Drucker, Donal O'Shea, Michael Brenner
Adipose-resident invariant natural killer T (iNKT) cells are key players in metabolic regulation. iNKT cells are innate lipid sensors, and their activation, using their prototypic ligand α-galactosylceramide (αGalCer), induces weight loss and restores glycemic control in obesity. Here, iNKT activation induced fibroblast growth factor 21 (FGF21) production and thermogenic browning of white fat. Complete metabolic analysis revealed that iNKT cell activation induced increased body temperature, V02, VC02, and fatty acid oxidation, without affecting food intake or activity...
September 13, 2016: Cell Metabolism
Surya Panicker Rajeev, John Wilding
Glucagon-like peptide receptor agonists (GLP-1 RA) have multiple effects, including control of glycaemia via stimulation of insulin and suppression of glucagon secretion and reduction of adiposity by enhancing satiety, so are an attractive therapeutic option in type 2 diabetes management. Five GLP-1 RA are used currently and more are in development. The HbA1c reduction obtained varies from 1 to 2%; they reduce body weight by about 2-3kg when used to treat T2DM, while liraglutide results in greater weight loss at a higher dose and has recently been approved for the management of obesity...
September 1, 2016: Current Opinion in Pharmacology
John T McLaughlin, Shane McKie
Functional mapping of human brain activation has made it possible to understand how different nutrients in the gut impact on homeostatic and appetitive brain responses. Current data are limited, but nutrient-specific effects are observed, with differential responses to lipid and sugars. Responses are not a simple function of calorie intake. Gut hormones such as CCK, PYY, GLP-1 and ghrelin are implicated in these responses, but may not exert effects directly on the brain. Research is now addressing how these homeostatic signalling states (fasting/fed) interact with hedonic responses, such as those evoked by images of appealing food...
August 27, 2016: Current Opinion in Pharmacology
Ying Wang, Aleksey Lomakin, Sonoko Kanai, Rainer Alex, Sara Belli, Massimiliano Donzelli, George B Benedek
Hybrid incretin peptides are a new generation of drugs for the treatment of diabetes and obesity. Despite their biological potency, the effectiveness of these peptides as drugs is limited by their short circulation time in blood (typically within minutes). In this work, we show that lipid conjugated forms of a GLP-1/GIP/glucagon hybrid peptides stay in circulation for hours. We studied the oligomerization and albumin-binding of the unconjugated hybrid peptide as well as its lipidated variants. These lipidated peptides differ in the N-terminal mutation, the position of lipidation and the linkage to lipid...
November 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Helene Johannessen, David Revesz, Yosuke Kodama, Nikki Cassie, Karolina Skibicka, Perry Barrett, Suzanne Dickson, Jens Holst, Jens Rehfeld, Geoffrey van der Plasse, Roger Adan, Bård Kulseng, Elinor Ben-Menachem, Chun-Mei Zhao, Duan Chen
BACKGROUND: Recently, the US FDA has approved "vagal blocking therapy or vBLoc® therapy" as a new treatment for obesity. The aim of the present study was to study the mechanism-of-action of "VBLOC" in rat models. METHODS: Rats were implanted with VBLOC, an intra-abdominal electrical device with leads placed around gastric vagal trunks through an abdominal incision and controlled by wireless device. Body weight, food intake, hunger/satiety, and metabolic parameters were monitored by a comprehensive laboratory animal monitoring system...
August 30, 2016: Obesity Surgery
R Sekar, K Singh, A W R Arokiaraj, B K C Chow
Glucagon family of peptide hormones is a group of structurally related brain-gut peptides that exert their pleiotropic actions through interactions with unique members of class B1 G protein-coupled receptors (GPCRs). They are key regulators of hormonal homeostasis and are important drug targets for metabolic disorders such as type-2 diabetes mellitus (T2DM), obesity, and dysregulations of the nervous systems such as migraine, anxiety, depression, neurodegeneration, psychiatric disorders, and cardiovascular diseases...
2016: International Review of Cell and Molecular Biology
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