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Sodium glucose linked transport

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https://www.readbyqxmd.com/read/29145743/novel-avenues-for-drug-discovery-in-diabetic-kidney-disease
#1
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...
November 16, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29137588/sodium-glucose-linked-transporter-2-inhibitor-associated-perioperative-euglycaemic-diabetic-ketoacidosis-a-case-for-a-perioperative-guideline
#2
C Hoffman, M Green, O Megafu
No abstract text is available yet for this article.
November 2017: Anaesthesia and Intensive Care
https://www.readbyqxmd.com/read/29126986/functional-redundancy-of-glucose-acquisition-mechanisms-in-the-hindgut-of-pacific-hagfish-eptatretus-stoutii
#3
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/cm(2)/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...
November 7, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/29039237/sglt2-inhibitors-are-they-safe
#4
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...
October 27, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28894748/new-antihyperglycemic-drugs-and-heart-failure-synopsis-of-basic-and-clinical-data
#5
REVIEW
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
https://www.readbyqxmd.com/read/28861731/adaptation-of-intestinal-and-bile-acid-physiology-accompany-the-metabolic-benefits-following-ileal-interposition-in-the-rat
#6
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
https://www.readbyqxmd.com/read/28835229/does-dapagliflozin-regress-left-ventricular-hypertrophy-in-patients-with-type-2-diabetes-a-prospective-double-blind-randomised-placebo-controlled-study
#7
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
https://www.readbyqxmd.com/read/28534922/fiber-purified-extracts-of-carob-fruit-decrease-carbohydrate-absorption
#8
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
https://www.readbyqxmd.com/read/28395981/mechanisms-linking-empagliflozin-to-cardiovascular-and-renal-protection
#9
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...
March 23, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28387957/molecular-interaction-of-anti-diabetic-drugs-with-acetylcholinesterase-and-sodium-glucose-co-transporter-2
#10
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)...
April 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28379501/cardiovascular-effects-of-urate-lowering-therapies-in-patients-with-chronic-gout-a-systematic-review-and-meta-analysis
#11
REVIEW
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
https://www.readbyqxmd.com/read/28358310/intestinal-transport-characteristics-and-metabolism-of-c-glucosyl-dihydrochalcone-aspalathin
#12
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
https://www.readbyqxmd.com/read/28295962/improving-glycaemic-control-in-type-2-diabetes-stimulate-insulin-secretion-or-provide-beta-cell-rest
#13
REVIEW
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
https://www.readbyqxmd.com/read/28255241/an-evidence-based-practice-oriented-review-focusing-on-canagliflozin-in-the-management-of-type-2-diabetes
#14
REVIEW
Joseph A Messana, Stanley S Schwartz, Raymond R Townsend
Caring for patients with type 2 diabetes mellitus (T2DM) has entered an era with many recent additions to the regimens used to clinically control their hyperglycemia. The most recent class of agents approved by the Food and Drug Administration (FDA) for T2DM is the sodium-glucose-linked transporter type 2 (SGLT2) inhibitors, which work principally in the proximal tubule of the kidney to block filtered glucose reabsorption. In the few years attending this new class arrival in the market, there has been a great deal of interest generated by the novel mechanism of action of SGLT2 inhibitors and by recent large outcome trials suggesting benefit on important clinical outcomes such as death, cardiovascular disease and kidney disease progression...
2017: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/28244693/dapagliflozin-improves-insulin-resistance-and-glucose-intolerance-in-a-novel-transgenic-rat-model-of-chronic-glucose-overproduction-and-glucose-toxicity
#15
Christos N Joannides, Salvatore P Mangiafico, Matthew F Waters, Benjamin J Lamont, Sofianos Andrikopoulos
AIM: To determine whether the excretion of glucose improves insulin resistance, impaired insulin secretion or both. MATERIALS AND METHODS: Appropriate methods were used to assess insulin sensitivity (euglycaemic-hyperinsulinaemic clamp) and insulin secretion (hyperglycaemic clamp) in insulin-resistant and hyperglycaemic phosphoenolpyruvate carboxykinase (PEPCK) transgenic rats after treatment with the sodium-glucose co-transporter-2 (SGLT2) inhibitor dapagliflozin...
August 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28242634/ketone-body-infusion-with-3-hydroxybutyrate-reduces-myocardial-glucose-uptake-and-increases-blood-flow-in-humans-a-positron-emission-tomography-study
#16
Lars C Gormsen, Mads Svart, Henrik Holm Thomsen, Esben Søndergaard, Mikkel H Vendelbo, Nana Christensen, Lars Poulsen Tolbod, Hendrik Johannes Harms, Roni Nielsen, Henrik Wiggers, Niels Jessen, Jakob Hansen, Hans Erik Bøtker, Niels Møller
BACKGROUND: High levels of ketone bodies are associated with improved survival as observed with regular exercise, caloric restriction, and-most recently-treatment with sodium-glucose linked transporter 2 inhibitor antidiabetic drugs. In heart failure, indices of ketone body metabolism are upregulated, which may improve energy efficiency and increase blood flow in skeletal muscle and the kidneys. Nevertheless, it is uncertain how ketone bodies affect myocardial glucose uptake and blood flow in humans...
February 27, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28241822/effects-of-canagliflozin-a-sodium-glucose-co-transporter-2-inhibitor-on-blood-pressure-and-markers-of-arterial-stiffness-in-patients-with-type-2-diabetes-mellitus-a-post-hoc-analysis
#17
RANDOMIZED CONTROLLED TRIAL
Michael Pfeifer, Raymond R Townsend, Michael J Davies, Ujjwala Vijapurkar, Jimmy Ren
BACKGROUND: Physiologic determinants, such as pulse pressure [difference between systolic blood pressure (SBP) and diastolic BP (DBP)], mean arterial pressure (2/3 DBP + 1/3 SBP), and double product [beats per minute (bpm) × SBP], are linked to cardiovascular outcomes. The effects of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, on pulse pressure, mean arterial pressure, and double product were assessed in patients with type 2 diabetes mellitus (T2DM). METHODS: This post hoc analysis was based on pooled data from four 26-week, randomized, double-blind, placebo-controlled studies evaluating canagliflozin in patients with T2DM (N = 2313) and a 6-week, randomized, double-blind, placebo-controlled, ambulatory BP monitoring (ABPM) study evaluating canagliflozin in patients with T2DM and hypertension (N = 169)...
February 27, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28214518/potentiating-slc-transporter-activity-emerging-drug-discovery-opportunities
#18
REVIEW
Marie-Laure Rives, Jonathan A Javitch, Alan D Wickenden
Maintaining the integrity of cellular membranes is critical to protecting metabolic activities and genetic information from the environment. Regulation of transport across membranes of essential chemicals, including water, nutrients, hormones and many drugs, is therefore key to cellular homeostasis and physiological processes. The two main transporter superfamilies are ATP-binding cassette (ABC) transporters that primarily function as efflux transporters, and the solute carrier (SLC) transporters. SLC transporters encompass 52 gene families with almost 400 different human transporter genes...
July 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28203358/the-renal-effects-of-sglt2-inhibitors-and-a-mini-review-of-the-literature
#19
REVIEW
Vasileios Andrianesis, Spyridoula Glykofridi, John Doupis
Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a new and promising class of antidiabetic agents which target renal tubular glucose reabsorption. Their action is based on the blockage of SGLT2 sodium-glucose cotransporters that are located at the luminal membrane of tubular cells of the proximal convoluted tubule, inducing glucosuria. It has been proven that they significantly reduce glycated hemoglobin (HbA1c), along with fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus (T2DM)...
December 2016: Therapeutic Advances in Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28193781/real-time-imaging-of-sodium-glucose-transporter-sglt1-trafficking-and-activity-in-single-cells
#20
Chiara Ghezzi, Guillaume Calmettes, Pauline Morand, Bernard Ribalet, Scott John
The processes controlling targeting of glucose transporters to apical and basolateral membranes of polarized cells are complex and not-well understood. We have engineered SGLT1 and GLUT4 constructs linked to fluorescent proteins to highlight the differences in transporter expression and trafficking, in real time, in different cell types. Activity was assessed in parallel using a FRET glucose sensor. In COS cells and HEK cells, SGLT1 was distributed between the plasma membrane and intracellular compartments, but there was little expression in CHO cells...
February 2017: Physiological Reports
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