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David Holmes
No abstract text is available yet for this article.
October 17, 2016: Nature Reviews. Endocrinology
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...
October 3, 2016: Journal of Internal Medicine
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
Vasilios G Athyros, Niki Katsiki, Asterios Karagiannis
No abstract text is available yet for this article.
September 9, 2016: Current Vascular Pharmacology
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
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
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
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
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
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
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
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...
July 27, 2016: Diabetes, Obesity & Metabolism
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 (T2DM) which may lead to bronchial hyperersponsiveness (BHR). Since glucagon-like peptide 1 regulates glucose homeostasis, we pharmacologically investigated the influence of the glucagon-like peptide 1 receptor (GLP1-R) agonist exendin-4 on the bronchial 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 asthmatic and diabetic patients, respectively...
July 22, 2016: American Journal of Respiratory Cell and Molecular Biology
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
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
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)
Marie L Davies, David Q Pham, Scott R Drab
Adding glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to basal insulin regimens has become a guideline-recommended treatment option for uncontrolled type 2 diabetes. However, limited data exist to support the use of GLP-1 RAs with insulin regimens, including bolus insulin in patients with type 2 diabetes. The primary objectives of this review were to identify if the combination of a GLP-1 RA and an insulin regimen containing bolus insulin resulted in improvements in HbA1c , weight loss, reduction in insulin doses, and to evaluate the side effect profile of this combination in terms of nausea and hypoglycemia risk...
August 2016: Pharmacotherapy
Roberto Carnevale, Lorenzo Loffredo, Maria Del Ben, Francesco Angelico, Cristina Nocella, Andreina Petruccioli, Simona Bartimoccia, Roberto Monticolo, Edda Cava, Francesco Violi
BACKGROUND & AIMS: Extra virgin olive oil (EVOO) improves post-prandial glycaemia in healthy subjects but it has never been investigated if this can be detected in pre-diabetic patients. We investigated if EVOO affects post-prandial glucose and lipid profile in patients with impaired fasting glucose (IFG). METHODS: Thirty IFG patients were randomly allocated to a meal containing or not 10 g of EVOO in a cross-over design. Before, 60 min and 120 min after lunch a blood sample was taken to measure glucose, insulin, Glucagon-like peptide-1 (GLP1), dipeptidyl-peptidase-4 (DPP4) activity, triglycerides (TG), total cholesterol, HDL-cholesterol and Apo B-48...
May 28, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Jana Jiráčková, Alena Šmahelová
Victoza (liraglutide) is a modern antidiabetic drug of GLP1 (glucagone like peptide) analogue group; since 2009 registered in Czech republic. VICTOZA is used in therapy of type 2 diabetic patients with preserved endougenous insulin secretion, usually in combination with other peroral antidiabetic drugs or with basal insulin. VICTOZA is applied once a day subcutaneously. The characteristical antidiabetic effect with β cell protection is enhanced with supportive weigth reduction effect. Positive cardiovascular influence is expected, however data from recent studies are not available at this time...
March 2016: Vnitr̆ní Lékar̆ství
Rodolfo Farlora, Valentina Valenzuela-Muñoz, Jacqueline Chávez-Mardones, Cristian Gallardo-Escárate
Aquaporins are small integral membrane proteins that function as pore channels for the transport of water and other small solutes across the cell membrane. Considering the important roles of these proteins in several biological processes, including host-parasite interactions, there has been increased research on aquaporin proteins recently. The present study expands on the knowledge of aquaporin family genes in parasitic copepods, examining diversity and expression during the ontogeny of the sea louse Caligus rogercresseyi...
July 1, 2016: Gene
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