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Sodium glucose linked transport

A H Heald, A A Fryer, S G Anderson, M Livingston, M Lunt, M Davies, Gyc Moreno, R Gadsby, R J Young, M Stedman
AIMS: Despite increasing spend on new Type 2 diabetes mellitus (T2DM) therapies, the proportion of people with T2DM achieving target glycaemia outcomes is declining. Our aim was to determine, using published General Practice level data, how differences in T2DM prescribing patterns relate to glycaemic target achievement levels. METHODS: Multiple linear regression modelling was used to link practice characteristics and defined daily dose (DDD) of class of medication in 2015/16 and changes to 2014/15 in medication to proportions achieving target glycaemic control (TGC; glycated haemoglobin A1c (HbA1c) ≤7...
March 8, 2018: Diabetes, Obesity & Metabolism
Stefanie Klinger, Gerhard Breves
BACKGROUND: Beneficial effects of Resveratrol (RSV) have been demonstrated, including effects on transporters and channels. However, little is known about how RSV influences intestinal transport. The aim of this study was to further characterize the effects of RSV on intestinal transport and the respective mechanisms. METHODS: Porcine jejunum and ileum were incubated with RSV (300 µM, 30 min) in Ussing chambers (functional studies) and tissue bathes (detection of protein expression, phosphorylation, association with detergent resistant membranes (DRMs))...
March 3, 2018: Nutrients
Christopher S Wilcox, Wen Shen, David W Boulton, Bruce R Leslie, Steven C Griffen
BACKGROUND: Dapagliflozin inhibits the sodium-glucose-linked transporter 2 in the renal proximal tubule, thereby promoting glycosuria to reduce hyperglycemia in type 2 diabetes mellitus. Because these patients may require loop diuretics, and sodium-glucose-linked transporter 2 inhibition causes an osmotic diuresis, we evaluated the diuretic interaction between dapagliflozin and bumetanide. METHODS AND RESULTS: Healthy subjects (n=42) receiving a fixed diet with ≈110 mmol·d-1 of Na+ were randomized to bumetanide (1 mg·d-1 ), dapagliflozin (10 mg·d-1 ), or both for 7 days, followed by 7 days of both...
February 10, 2018: Journal of the American Heart Association
Cristina Otero-Rodiño, Ana Rocha, Rosa Álvarez-Otero, Rosa M Ceinos, Marcos A López-Patiño, Jesús M Míguez, José Miguel Cerdá-Reverter, José L Soengas
To assess the hypothesis of glucosensing systems present in fish telencephalon, we first demonstrated in rainbow trout by in situ hybridization the presence of glucokinase (GK). Then, we assessed the response of glucosensing markers in rainbow trout telencephalon 6h after ICV treatment with glucose or 2-deoxyglucose (inducing glucoprivation). We evaluated the response of parameters related to the mechanisms dependent on GK, liver X receptor (LXR), mitochondrial activity, sweet taste receptor, and sodium-glucose linked transporter 1 (SGLT-1)...
February 10, 2018: Journal of Neuroendocrinology
A Balakrishnan
Short bowel syndrome occurs following the loss of a large portion of functional intestine and is associated with high morbidity and mortality. The intestine exhibits pronounced diurnal rhythms in glucose absorption and mounts a profound proliferative response following massive small bowel resection. Understanding the molecular pathways that underpin this could yield novel treatment options. Two in vivo models were employed using the nocturnally active Sprague Dawley® rat, namely daytime feeding and massive small bowel resection...
January 24, 2018: Annals of the Royal College of Surgeons of England
Chun-Ying Li, Liang-Xue Wang, Si-Si Dong, Ying Hong, Xin-He Zhou, Wen-Wen Zheng, Chao Zheng
BACKGROUND Sodium glucose transporter-2 inhibitors are the newest antidiabetic drugs that seem to be cardioprotective and can prevent type 2 diabetes in patients with high cardiovascular risks. Previous clinical trials have shown that these inhibitors can alleviate endothelial dysfunction, but the mechanism of action remains unknown. How SGLT inhibitor influences the release of NO in PA-induced HUVECs has never been reported. MATERIAL AND METHODS To explore the potential effects of the endothelial-protective mechanism of phlorizin and its impact on nitric oxide (NO), human umbilical vein endothelial cells (HUVECs) were incubated with palmitic acid (PA) and then treated with phlorizin...
January 8, 2018: Medical Science Monitor Basic Research
Liuqing Xu, Yingfeng Shi, Shougang Zhuang, Na Liu
Uric acid is the product of purine metabolism and its increased levels result in hyperuricemia. A number of epidemiological reports link hyperuricemia with multiple disorders, such as kidney diseases, cardiovascular diseases and diabetes. Recent studies also showed that expression and functional changes of urate transporters are associated with hyperuricemia. Uric acid transporters are divided into two categories: urate reabsorption transporters, including urate anion transporter 1 (URAT1), organic anion transporter 4 (OAT4) and glucose transporter 9 (GLUT9), and urate excretion transporetrs, including OAT1, OAT3, urate transporter (UAT), multidrug resistance protein 4 (MRP4/ABCC4), ABCG-2 and sodium-dependent phosphate transport protein...
November 21, 2017: Oncotarget
Matthew D Breyer, Matthias Kretzler
Diabetic kidney disease (DKD) has emerged as major cause of morbidity and mortality. After progressing to renal failure, over 70% of DKD patients are dead with five years. New treatments to slow this progression are desperately needed. Areas covered: This review highlights the current treatment options for people with DKD with a particular focus on angiotensin pathway blockade and the potential use of sodium glucose linked transporter 2 (SGLT2) inhibitors. These treatments are associated with an initial decrease in glomerular filtration rate (GFR) and albuminuria; there is also attention on renal hyperfiltration as therapeutic target...
January 2018: Expert Opinion on Drug Discovery
C Hoffman, M Green, O Megafu
No abstract text is available yet for this article.
November 2017: Anaesthesia and Intensive Care
Alyssa M Weinrauch, Alexander M Clifford, Greg G Goss
This study examined the mechanisms of glucose acquisition in the hindgut of Pacific hagfish (Eptatretus stoutii) using in vitro gut sac techniques. The intestine was determined to have the capacity to digest maltose into glucose along the entirety of the tract, including the foregut. Glucose uptake was biphasic and consisted of a high-affinity, low-capacity concentration-dependent component conforming to Michaelis-Menten kinetics (Km 0.37mM, Jmax 8.48nmol/cm2 /h) as well as a diffusive component. There was no observed difference in glucose flux rate along the length of the intestine, similar to other nutrients investigated in the hagfish intestine...
February 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Sebastian Filippas-Ntekouan, Theodosios D Filippatos, Moses S Elisaf
Sodium-glucose linked transporter type 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs with positive cardiovascular and kidney effects. The aim of this review is to present the safety issues associated with SGLT2 inhibitors. Urogenital infections are the most frequently encountered adverse events, although tend to be mild to moderate and are easily manageable with standard treatment. Although no increased acute kidney injury risk was evident in the major trials, the mechanism of action of these drugs requires caution when they are administered in patients with extracellular volume depletion or with drugs affecting renal hemodynamics...
January 2018: Postgraduate Medicine
Dirk von Lewinski, Ewald Kolesnik, Markus Wallner, Michael Resl, Harald Sourij
The assessment of the cardiovascular safety profile of any newly developed antihyperglycemic drug is mandatory before registration, as a meta-analysis raised alarm describing a significant increase in myocardial infarction with the thiazolidinedione rosiglitazone. The first results from completed cardiovascular outcome trials are already available: TECOS, SAVOR-TIMI, and EXAMINE investigated dipeptidyl peptidase 4 (DPP-4) inhibitors, ELIXA, LEADER, and SUSTAIN-6 investigated glucagon-like peptide 1 (GLP-1) receptor agonists, and EMPA-REG OUTCOME and CANVAS investigated sodium-dependent glucose transporter 2 (SGLT-2) inhibitors...
2017: BioMed Research International
Ping Zhao, Donna Wendt, Sean Z Goodin, Shwetha Ravichandran, Tara E Chouinard, April D Strader
PURPOSE: Ileal interposition recapitulates many of the metabolic improvements similar to Roux-en-Y gastric bypass. We aimed to determine whether the metabolic improvements seen following ileal interposition were conferred solely by the interposed segment by examining changes in neighboring intestinal segments as well as the composition of the bile acid pool. MATERIALS AND METHODS: Adult male rats were treated with either sham or ileal interposition surgeries. Glucose tolerance tests, body composition analysis, polymer chain reaction, enzyme-linked immunosorbent assay, and mass spectrometry were done after the surgeries...
August 31, 2017: Obesity Surgery
Alexander J M Brown, Chim Lang, Rory McCrimmon, Allan Struthers
BACKGROUND: Patients with diabetes have a two to fourfold increased risk for development of and death from cardiovascular disease [CVD]. The current oral hypoglycaemic agents result in limited reduction in this cardiovascular risk. Sodium glucose linked co-transporter type 2 [SGLT2] inhibitors are a relatively new class of antidiabetic agent that have been shown to have potential cardiovascular benefits. In support of this, the EMPA-REG trial showed a striking 38% and 35% reduction in cardiovascular mortality and heart failure [HF] hospitalisation respectively...
August 23, 2017: BMC Cardiovascular Disorders
A Macho-González, A Garcimartín, M E López-Oliva, G Bertocco, F Naes, S Bastida, F J Sánchez-Muniz, J Benedí
The postprandial state plays a central role in the development and setting of chronic diseases. Condensed tannins (CT) are polyphenols with a known ability to modify carbohydrate digestion and absorption. The high concentration of CT in the pulp of carob fruit suggests a potential antidiabetic effect. The aim of this work was to analyze the in vitro and in vivo effects of carob fruit extract (CFE) on the digestion and absorption of carbohydrates. α-Glucosidase activity and glucose diffusion were tested in vitro using 0...
June 21, 2017: Food & Function
Pasquale Perrone-Filardi, Angelo Avogaro, Enzo Bonora, Furio Colivicchi, Paola Fioretto, Aldo Pietro Maggioni, Giorgio Sesti, Ele Ferrannini
In patients with type 2 diabetes mellitus (T2DM), the main cause of morbidity and mortality is cardiovascular (CV) disease. Diabetic kidney disease, which develops in approximately 40% of patients with T2DM, further increases the risk of CV-related morbidity and mortality. The sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin, which provides effective glycaemic control as either monotherapy or as an add-on to other glucose-lowering agents in patients with T2DM, was also shown to improve CV and renal outcomes in the large, randomised, placebo-controlled EMPA-REG OUTCOME trial in patients with T2DM at high risk of CV events...
August 15, 2017: International Journal of Cardiology
Shazi Shakil
Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease (AD) are the two disorders which are known to share pertinent pathological and therapeutic links. Sodium glucose co-transporter-2 (SGLT2) and Acetylcholinesterase (AChE) are established inhibition targets for T2DM and AD treatments, respectively. Reports suggest that anti-diabetic drugs could be used for AD treatment also. The present study used molecular docking by Autodock4.2 using our "Click-By-Click"-protocol, Ligplot1.4.3 and "change in accessible surface area (ΔASA)-calculations" to investigate the binding of two investigational anti-diabetic drugs, Ertugliflozin and Sotagliflozin to an established target (SGLT2) and a research target (human brain AChE)...
November 2017: Journal of Cellular Biochemistry
Tony Zhang, Janet E Pope
Objectives: To determine if urate-lowering treatment (ULT) in gout can reduce cardiovascular (CV) outcomes. Methods: Randomized trials were searched for treatment with ULT in gout. Eligible trials had to report CV safety of a ULT. Potential medications included allopurinol, febuxostat, pegloticase, rasburicase, probenecid, benzbromarone, sulphinpyrazone, losartan, fenofibrate and sodium-glucose linked transporter 2 inhibitors. Results: A total of 3084 citations were found, with 642 duplicates...
July 1, 2017: Rheumatology
Sandra Bowles, Elizabeth Joubert, Dalene de Beer, Johan Louw, Christel Brunschwig, Mathew Njoroge, Nina Lawrence, Lubbe Wiesner, Kelly Chibale, Christo Muller
Insight into the mechanisms of intestinal transport and metabolism of aspalathin will provide important information for dose optimisation, in particular for studies using mouse models. Aspalathin transportation across the intestinal barrier (Caco-2 monolayer) tested at 1-150 µM had an apparent rate of permeability (Papp) typical of poorly absorbed compounds (1.73 × 10(-6) cm/s). Major glucose transporters, sodium glucose linked transporter 1 (SGLT1) and glucose transporter 2 (GLUT2), and efflux protein (P-glycoprotein, PgP) (1...
March 30, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Daniël H van Raalte, C Bruce Verchere
Type 2 diabetes (T2D) is characterized by a gradual decline in pancreatic beta cell function that determines the progressive course of the disease. While beta-cell failure is an important contributor to hyperglycaemia, chronic hyperglycaemia itself is also detrimental for beta-cell function, probably by inducing prolonged secretory stress on the beta cell as well as through direct glucotoxic mechanisms that have not been fully defined. For years, research has been carried out in search of therapies targeting hyperglycaemia that preserve long-term beta-cell function in T2D, a quest that is still ongoing...
September 2017: Diabetes, Obesity & Metabolism
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