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https://www.readbyqxmd.com/read/27903028/-cardiovascular-morbidity-and-mortality-in-patients-with-kidney-disease
#1
Ivo Quack, Ralf Westenfeld
Patients with kidney disease have a significantly increased cardiovascular morbidity and mortality. Especially diabetics have an increased risk to develop renal insufficiency and cardiovascular events. Two recent studies show that the SGLT2 inhibitor Empagliflozin and the GLP1 agonist Liraglutid are able to lower the cardiovascular risk of type2 diabetics with renal insufficiency. Recent observations suggest that bradycardia and asystole are main triggers for sudden cardiac death in patients with chronic kidney disease...
November 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27898183/effect-of-exenatide-on-postprandial-glucose-fluxes-lipolysis-and-%C3%A3-cell-function-in-nondiabetic-morbidly-obese-patients
#2
Stefania Camastra, Brenno Astiarraga, Andrea Tura, Silvia Frascerra, Demetrio Ciociaro, Andrea Mari, Amalia Gastaldelli, Ele Ferrannini
AIMS: To investigate the effect of exenatide on glucose disposal, insulin secretion, ß-cell function, lipolysis, and hormone concentrations in non-diabetic, morbidly obese subjects under physiological conditions. MATERIALS AND METHODS: Patients were assigned to exenatide 10 µg twice daily (EXE, n = 15) or control (CT, n = 15) for 3 months. Patients received a meal test/tracer study (MTT) to measure endogenous glucose production (EGP), rate of oral glucose appearance (RaO), insulin secretion rate (ISR), ß-cell function, hepatic (HIR) and adipose tissue insulin resistance (AT-IR) and insulin sensitivity (IS)...
November 29, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27872157/exendin-4-increases-oxygen-consumption-and-thermogenic-gene-expression-in-muscle-cells
#3
Jin-Seung Choung, Young-Sun Lee, Hee-Sook Jun
Glucagon-like peptide-1 (GLP1) has many anti-diabetic actions and also increases energy expenditure in vivo. Since skeletal muscle is a major organ controlling energy metabolism, we investigated whether GLP1 can affect energy metabolism in muscle. We found that treatment of differentiated C2C12 cells with Exendin-4 (Ex-4), a GLP1 receptor agonist, reduced oleate:palmitate-induced lipid accumulation and triglyceride content compared with cells without Ex-4 treatment. When we examined the oxygen consumption rate (OCR), not only the basal OCR but also the OCR induced by oleate:palmitate addition was significantly increased in Ex-4-treated differentiated C2C12 cells, and this was inhibited by Exendin-9, a GLP1 receptor antagonist...
November 21, 2016: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27780892/diabetes-negatively-affects-cortical-and-striatal-gabaergic-neurons-an-effect-that-is-partially-counteracted-by-exendin-4
#4
Martin Larsson, Grazyna Lietzau, David Nathanson, Claes-Göran Östenson, Carina Mallard, Maria E Johansson, Thomas Nyström, Cesare Patrone, Vladimer Darsalia
Type 2 diabetic (T2D) patients often develop early cognitive and sensorimotor impairments. The pathophysiological mechanisms behind these problems are largely unknown. Recent studies demonstrate that dysfunctional γ-Aminobutyric acid (GABAergic) neurons are involved in age-related cognitive decline. We hypothesized that similar, but earlier dysfunction is taking place under T2D in the neocortex and striatum (two brain areas important for cognition and sensorimotor functions). We also hypothesized that the T2D-induced effects are pharmacologically reversible by anti-diabetic drugs targeting the glucagon-like peptide-1 receptor (GLP-1R)...
October 25, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27748385/adipose-tissue-key-role-for-fgf21-in-glp1-mediated-weight-loss
#5
David Holmes
No abstract text is available yet for this article.
December 2016: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/27699898/adipose-tissue-regulates-insulin-sensitivity-role-of-adipogenesis-de-novo-lipogenesis-and-novel-lipids
#6
U Smith, B B Kahn
Obesity, the major cause of the current global epidemic of type 2 diabetes (T2D), induces insulin resistance in peripheral insulin target tissues. Several mechanisms have been identified related to cross-talk between adipose tissue, skeletal muscle and liver. These mechanisms involve both increased free fatty acid release and altered secretion of adipokines from adipose tissue. A major determinant of metabolic health is the ability of subcutaneous adipose tissue (SAT) to store excess fat rather than allowing it to accumulate in ectopic depots including liver (i...
November 2016: Journal of Internal Medicine
https://www.readbyqxmd.com/read/27689014/fibroblast-activation-protein-fap-as-a-novel-metabolic-target
#7
Miguel Angel Sánchez-Garrido, Kirk M Habegger, Christoffer Clemmensen, Cassie Holleman, Timo D Müller, Diego Perez-Tilve, Pengyun Li, Archita S Agrawal, Brian Finan, Daniel J Drucker, Matthias H Tschöp, Richard D DiMarchi, Alexei Kharitonenkov
OBJECTIVE: Fibroblast activation protein (FAP) is a serine protease belonging to a S9B prolyl oligopeptidase subfamily. This enzyme has been implicated in cancer development and recently reported to regulate degradation of FGF21, a potent metabolic hormone. Using a known FAP inhibitor, talabostat (TB), we explored the impact of FAP inhibition on metabolic regulation in mice. METHODS: To address this question we evaluated the pharmacology of TB in various mouse models including those deficient in FGF21, GLP1 and GIP signaling...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27633289/can-glucagon-like-peptide-1-glp1-agonists-or-sodium-glucose-co-transporter-2-sglt2-inhibitors-ameliorate-non-alcoholic-steatohepatitis-in-people-with-or-without-diabetes
#8
Vasilios G Athyros, Niki Katsiki, Asterios Karagiannis
No abstract text is available yet for this article.
September 9, 2016: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/27627094/-glucagon-antagonists-open-a-new-way-in-treatment-of-type-2-diabetes-mellitus
#9
Karel Vondra
UNLABELLED: Excessive hepatic glucose production resulting from dysregulated glucagon secretion associated with inappropriate fasting and postprandial hyperglucagonemia is common feature in type 2 diabetes (DM2T). The effects of some currently widely used anti-diabetic agents, especially concerning metformin, GLP1 agonists and inhibitors of DPP4, comprise partial supression of glucagon secretion and/or action. Complete supression of glucagon action is recently widely investigated in experiments, and also results of phase 1 and 2 of the clinical trials are available...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27593966/inkt-cells-induce-fgf21-for-thermogenesis-and-are-required-for-maximal-weight-loss-in-glp1-therapy
#10
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
https://www.readbyqxmd.com/read/27591963/novel-developments-in-vagal-afferent-nutrient-sensing-and-its-role-in-energy-homeostasis
#11
Guillaume de Lartigue, Charlene Diepenbroek
Vagal afferent neurons (VANs) play an important role in the control of food intake by signaling nutrient type and quantity to the brain. Recent findings are broadening our view of how VANs impact not only food intake but also energy homeostasis. This review focuses exclusively on studies of the vagus nerve from the past 2 years that highlight major new advancements in the field. We firstly discuss evidence that VANs can directly sense nutrients, and we consider new insights into mechanisms affecting sensing of gastric distension and signaling by gastrointestinal hormones ghrelin and GLP1...
September 1, 2016: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/27577947/gut-microbiota-of-obese-type-2-diabetic-individuals-is-enriched-in-faecalibacterium-prausnitzii-akkermansia-muciniphila-and-peptostreptococcus-anaerobius-after-weight-loss
#12
Marlene Remely, Berit Hippe, Julia Zanner, Eva Aumueller, Helmuth Brath, Alexander G Haslberger
Beside the influence of nutritional habits and reduced physical activity, metabolic syndrome is associated with alterations in the structure of gut microbiota influencing the inflammatory immune responses. Gut microbiota and microbial metabolic activities are known to affect the lipid and glucose metabolism, satiety and chronic low-grade inflammation in the metabolic syndrome. The aim of the study was to identify genera or even species affecting host metabolism in obesity and type 2 diabetes beside the commonly used indicator: Firmicutes/Bacteroidetes ratio...
August 30, 2016: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/27533760/gliptins-and-their-target-dipeptidyl-peptidase-4-implications-for-the-treatment-of-vascular-disease
#13
REVIEW
Friederike Remm, Wolfgang-Michael Franz, Christoph Brenner
Gliptins are accepted as a standard therapy for diabetes mellitus today. By inhibition of the enzyme dipeptidyl peptidase 4 (DPP4), gliptins prolong the GLP1-dependent insulin secretion in the pancreatic β-cells and thus support physiological blood glucose control. Various studies have now raised hope for an additional protective effect of pharmacological DPP4 inhibition in vascular diseases. Besides GLP1, especially, the inhibition of SDF1 cleavage has been shown to depict a relevant mechanism to enhance endothelial regeneration and reduce atherosclerosis progression via the SDF1-CXCR4 axis...
July 2016: European Heart Journal. Cardiovascular Pharmacotherapy
https://www.readbyqxmd.com/read/27526057/99mtc-labeled-glucagon-like-peptide-1-analogue-99mtc-glp1-scintigraphy-in-the-management-of-patients-with-occult-insulinoma
#14
Anna Sowa-Staszczak, Małgorzata Trofimiuk-Müldner, Agnieszka Stefańska, Monika Tomaszuk, Monika Buziak-Bereza, Aleksandra Gilis-Januszewska, Agata Jabrocka-Hybel, Bogusław Głowa, Maciej Małecki, Tomasz Bednarczuk, Grzegorz Kamiński, Aldona Kowalska, Renata Mikołajczak, Barbara Janota, Alicja Hubalewska-Dydejczyk
INTRODUCTION: The aim of this study was to assess the utility of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 scintigraphy in the management of patients with hypoglycemia, particularly in the detection of occult insulinoma. MATERIALS AND METHODS: Forty patients with hypoglycemia and increased/confusing results of serum insulin and C-peptide concentration and negative/inconclusive results of other imaging examinations were enrolled in the study. In all patients GLP-1 receptor imaging was performed to localise potential pancreatic lesions...
2016: PloS One
https://www.readbyqxmd.com/read/27474690/endocrine-effects-of-duodenal-jejunal-exclusion-in-obese-patients-with-type-2-diabetes-mellitus
#15
Petra Kaválková, Miloš Mráz, Pavel Trachta, Jana Kloučková, Anna Cinkajzlová, Zdeňka Lacinová, Denisa Haluzíková, Marek Beneš, Zuzana Vlasáková, Václav Burda, Daniel Novák, Tomáš Petr, Libor Vítek, Terezie Pelikánová, Martin Haluzík
Duodenal-jejunal bypass liner (DJBL) is an endoscopically implantable device designed to noninvasively mimic the effects of gastrointestinal bypass operations by excluding the duodenum and proximal jejunum from the contact with ingested food. The aim of our study was to assess the influence of DJBL on anthropometric parameters, glucose regulation, metabolic and hormonal profile in obese patients with type 2 diabetes mellitus (T2DM) and to characterize both the magnitude and the possible mechanisms of its effect...
October 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27460695/vascular-effects-of-linagliptin-in-non-obese-diabetic-mice-are-glucose-independent-and-involve-positive-modulation-of-the-endothelial-nitric-oxide-synthase-enos-caveolin-1-cav-1-pathway
#16
Valentina Vellecco, Emma Mitidieri, Antonella Gargiulo, Vincenzo Brancaleone, Danilo Matassa, Thomas Klein, Franca Esposito, Giuseppe Cirino, Mariarosaria Bucci
AIM: To test the effect of linagliptin in non-obese diabetic (NOD) mice, a murine model of type 1 diabetes, to unveil a possible direct cardiovascular action of dipeptidyl peptidase 4 (DPP-4) inhibitors beyond glycaemia control. METHODS: NOD mice were grouped according to glycosuria levels as NODI: none; NODII: high; NODIII: severe. Linagliptin treatment was initiated once they reached NODII levels. Vascular reactivity was assessed ex vivo on aorta harvested from mice upon reaching NODIII level...
December 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27447052/glucagon-like-peptide-1-receptor-a-novel-pharmacological-target-for-treating-human-bronchial-hyperresponsiveness
#17
Paola Rogliani, Luigino Calzetta, Barbara Capuani, Francesco Facciolo, Mario Cazzola, Davide Lauro, Maria Gabriella Matera
Asthma is associated with several comorbidities, such as type 2 diabetes mellitus, which may lead to bronchial hyperresponsiveness (BHR). Because glucagon-like peptide (GLP) 1 regulates glucose homeostasis, we pharmacologically investigated the influence of the GLP1 receptor (GLP1-R) agonist, exendin-4, on BHR induced in human isolated airways. The effect of exendin-4 was assessed in human isolated airways undergoing overnight passive sensitization and high-glucose stimulation, two conditions mimicking ex vivo the BHR typical of patients with asthma and diabetes, respectively...
December 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27431457/insulin-resistance-microbiota-and-fat-distribution-changes-by-a-new-model-of-vertical-sleeve-gastrectomy-in-obese-rats
#18
Nicola Basso, Emanuele Soricelli, Lidia Castagneto-Gissey, Giovanni Casella, Davide Albanese, Francesca Fava, Claudio Donati, Kieran Tuohy, Giulia Angelini, Federica La Neve, Anna Severino, Virginia Kamvissi-Lorenz, Andrea L Birkenfeld, Stefan Bornstein, Melania Manco, Geltrude Mingrone
Metabolic surgery improves insulin resistance and type 2 diabetes possibly because of weight loss. We performed a novel sleeve gastrectomy in rats that resects ∼80% of the glandular portion, leaving the forestomach almost intact (glandular gastrectomy [GG]) and compared subsequent metabolic remodeling with a sham operation. GG did not affect body weight, at least after 10 weeks; improved hepatic and peripheral insulin sensitivity likely through increased Akt, glycogen synthase kinase 3, and AMPK phosphorylation; and reduced ectopic fat deposition and hepatic glycogen overaccumulation...
October 2016: Diabetes
https://www.readbyqxmd.com/read/27373139/novel-antidiabetic-drugs-and-cardiovascular-risk-primum-non-nocere
#19
R C Bonadonna, C Borghi, A Consoli, M Volpe
AIMS: Diabetes treatments aim at preventing undesirable metabolic effects of hyperglycemia and at preventing/reducing tissue damage, including cardiovascular (CV) events. For approval, novel diabetes drugs undergo early systematic investigation to assess CV safety. This review provides an updated analysis of the results of recent studies examining novel diabetes medications and CV outcomes. DATA SYNTHESIS: The new regulatory guidelines enforce adjudication of all CV events when testing novel diabetes drugs...
September 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/27368005/comparative-effectiveness-of-incretin-based-therapies-and-the-risk-of-death-and-cardiovascular-events-in-38-233-metformin-monotherapy-users
#20
John-Michael Gamble, Jamie M Thomas, Laurie K Twells, William K Midodzi, Sumit R Majumdar
There is limited comparative effectiveness evidence to guide approaches to managing diabetes in individuals failing metformin monotherapy. Our aim was to compare the incidence of all-cause mortality and major adverse cardiovascular events (MACEs) among new metformin monotherapy users initiating a dipeptidyl-peptidase-4 inhibitor (DPP4i), glucagon-like peptide-1 receptor agonist (GLP-1RA), sulfonylurea (SU), thiazolidinedione, or insulin.We conducted a cohort study using the UK-based Clinical Practice Research Datalink...
June 2016: Medicine (Baltimore)
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