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Sodium glucose linked transport

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https://www.readbyqxmd.com/read/28395981/mechanisms-linking-empagliflozin-to-cardiovascular-and-renal-protection
#1
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
#2
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- (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
#3
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...
March 30, 2017: Rheumatology
https://www.readbyqxmd.com/read/28358310/intestinal-transport-characteristics-and-metabolism-of-c-glucosyl-dihydrochalcone-aspalathin
#4
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-glycemic-control-in-type-2-diabetes-stimulate-insulin-secretion-or-provide-beta-cell-rest
#5
REVIEW
Daniël H van Raalte, C Bruce Verchere
Type 2 diabetes (T2D) is characterized by a gradual decline of pancreatic beta cell function that determines the progressive course of the disease. While beta-cell failure is an important contributor to hyperglycemia, chronic hyperglycemia itself is also detrimental for beta-cell function, likely 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 hyperglycemia that preserve long-term beta-cell function in T2D, a quest that is still ongoing...
March 14, 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
#6
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-with-chronic-glucose-overproduction-and-glucose-toxicity
#7
Christos N Joannides, Salvatore P Mangiafico, Matthew F Waters, Benjamin J Lamont, Sofianos Andrikopoulos
AIMS: Insulin resistance and impaired insulin secretion are cardinal defects that contribute to hyperglycemia in type 2 diabetes. Recently, a new class of drugs called sodium-glucose linked transporter 2 (SGLT2) inhibitors has been introduced that reduce blood glucose by inhibiting glucose reabsorption in the kidney and is not dependent on glucose metabolism or insulin action. The purpose of the present study was to determine whether the excretion of glucose would improve insulin resistance, impaired insulin secretion or both...
February 28, 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
#8
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
#9
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
#10
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...
February 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28203358/the-renal-effects-of-sglt2-inhibitors-and-a-mini-review-of-the-literature
#11
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
#12
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
https://www.readbyqxmd.com/read/28170426/chronic-social-stress-in-pigs-impairs-intestinal-barrier-and-nutrient-transporter-function-and-alters-neuro-immune-mediator-and-receptor-expression
#13
Yihang Li, Zehe Song, Katelyn A Kerr, Adam J Moeser
Psychosocial stress is a major factor driving gastrointestinal (GI) pathophysiology and disease susceptibility in humans and animals. The mechanisms governing susceptibility to stress-induced GI disease remain poorly understood. In the present study, we investigated the influence of chronic social stress (CSS) in pigs, induced by 7 d of chronic mixing/crowding stress, on intestinal barrier and nutrient transport function, corticotropin releasing factor (CRF) signaling and immunological responses. Results from this study showed that CSS resulted in a significant impairment of ileal and colonic barrier function indicated by reduced transepithelial electrical resistance (TER) in the ileum and increased FD4 flux in the ileum (by 0...
2017: PloS One
https://www.readbyqxmd.com/read/27798769/distinct-glucose-lowering-mechanisms-of-ipragliflozin-depending-on-body-weight-changes
#14
Eiji Kutoh, Teruma Murayama, Asuka Wada, Mitsuru Hirate
BACKGROUND: Sodium-glucose co-transporter 2 inhibitors have been shown to reduce body weight. However, little is known about whether a reduction in body weight affects glycemic and non-glycemic parameters. OBJECTIVES: The aim of this study was to investigate the link between the changes in body weight and those in metabolic parameters in drug-naïve subjects with type 2 diabetes mellitus (T2DM) receiving ipragliflozin monotherapy. METHODS: Subjects received ipragliflozin monotherapy 25-50 mg/day for 3 months (n = 33)...
December 2016: Drugs in R&D
https://www.readbyqxmd.com/read/27765008/sglt2-inhibitors-in-diabetes-mellitus-treatment
#15
Juan Rosas-Guzmán, Juan Rosas-Saucedo, Alma R J Romero-García
Type 2 Diabetes Mellitus (T2DM) is a chronic illness with high prevalence in Mexico, Latin-America, and the world and is associated to high morbidity, disability, and mortality rate, especially in developing countries. T2DM physiopathology is very complex; insulin resistance in the muscle, liver, and adipose tissue, a reduction in the production of incretins (mainly GLP-1) in the intestine, increased glucagon synthesis, an insufficient response of insulin generation, and increased glucose reabsorption in the kidney lead all together to an hyperglycemic state, which has been closely associated with the development of micro and macrovascular complications...
August 29, 2016: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/27754289/br-08-1-high-sodium-intake-reduction-in-diabetes-with-hypertension
#16
Zhiming Zhu
Management of hypertension in diabetes is critical for reducing cardiovascular mortality and morbidity. Dietary approaches for controlling high blood pressure have historically focused on sodium. Thus, many guidelines recommend that patients with type 2 diabetes reduce high sodium intake. Nonetheless, the potential benefits of sodium reduction are debatable. The kidney has a crucial role in glucose filtration and reabsorption in addition to its regulation of fluid and electrolyte homeostasis. A key factor linking sodium uptake and glucose transport is the sodium-glucose cotransporter 2 (SGLT2) in renal proximal tubular cells...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27643287/br-08-1-high-sodium-intake-reduction-in-diabetes-with-hypertension
#17
Zhiming Zhu
Management of hypertension in diabetes is critical for reducing cardiovascular mortality and morbidity. Dietary approaches for controlling high blood pressure have historically focused on sodium. Thus, many guidelines recommend that patients with type 2 diabetes reduce high sodium intake. Nonetheless, the potential benefits of sodium reduction are debatable. The kidney has a crucial role in glucose filtration and reabsorption in addition to its regulation of fluid and electrolyte homeostasis. A key factor linking sodium uptake and glucose transport is the sodium-glucose cotransporter 2 (SGLT2) in renal proximal tubular cells...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27422625/research-into-the-effect-of-sglt2-inhibition-on-left-ventricular-remodelling-in-patients-with-heart-failure-and-diabetes-mellitus-reform-trial-rationale-and-design
#18
RANDOMIZED CONTROLLED TRIAL
Jagdeep S S Singh, Amir Fathi, Keeran Vickneson, Ify Mordi, Mohapradeep Mohan, J Graeme Houston, Ewan R Pearson, Allan D Struthers, Chim C Lang
BACKGROUND: Heart failure (HF) and diabetes (DM) are a lethal combination. The current armamentarium of anti-diabetic agents has been shown to be less efficacious and sometimes even harmful in diabetic patients with concomitant cardiovascular disease, especially HF. Sodium glucose linked co-transporter type 2 (SGLT2) inhibitors are a new class of anti-diabetic agent that has shown potentially beneficial cardiovascular effects such as pre-load and after load reduction through osmotic diuresis, blood pressure reduction, reduced arterial stiffness and weight loss...
July 15, 2016: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27273883/gastrointestinal-transport-of-calcium-and-glucose-in-lactating-ewes
#19
Stefanie Klinger, Bernd Schröder, Anja Gemmer, Julia Reimers, Gerhard Breves, Jens Herrmann, Mirja R Wilkens
During lactation, mineral and nutrient requirements increase dramatically, particularly those for Ca and glucose. In contrast to monogastric species, in ruminants, it is rather unclear to which extend this physiological change due to increased demand for milk production is accompanied by functional adaptations of the gastrointestinal tract (GIT). Therefore, we investigated potential modulations of Ca and glucose transport mechanisms in the GIT of lactating and dried-off sheep. Ussing-chamber technique was applied to determine the ruminal and jejunal Ca flux rates...
June 2016: Physiological Reports
https://www.readbyqxmd.com/read/27223826/mechanisms-involved-in-the-development-of-the-chronic-gastrointestinal-syndrome-in-nonhuman-primates-after-total-body-irradiation-with-bone-marrow-shielding
#20
Terez Shea-Donohue, Alessio Fasano, Aiping Zhao, Luigi Notari, Shu Yan, Rex Sun, Jennifer A Bohl, Neemesh Desai, Greg Tudor, Motoko Morimoto, Catherine Booth, Alexander Bennett, Ann M Farese, Thomas J MacVittie
In this study, nonhuman primates (NHPs) exposed to lethal doses of total body irradiation (TBI) within the gastrointestinal (GI) acute radiation syndrome range, sparing ∼5% of bone marrow (TBI-BM5), were used to evaluate the mechanisms involved in development of the chronic GI syndrome. TBI increased mucosal permeability in the jejunum (12-14 Gy) and proximal colon (13-14 Gy). TBI-BM5 also impaired mucosal barrier function at doses ranging from 10-12.5 Gy in both small intestine and colon. Timed necropsies of NHPs at 6-180 days after 10 Gy TBI-BM5 showed that changes in small intestine preceded those in the colon...
June 2016: Radiation Research
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