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Sodium cotransporter

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https://www.readbyqxmd.com/read/28535336/transport-of-the-glucosamine-derived-browning-product-fructosazine-polyhydroxyalkylpyrazine-across-the-human-intestinal-caco-2-cell-monolayer-role-of-the-hexose-transporters
#1
Abhishek Bhattacherjee, Yuliya Hrynets, Mirko Betti
The transport mechanism of fructosazine, a glucosamine self-condensation product, was investigated using a Caco-2 cell model. Fructosazine transport was assessed by measuring the bidirectional permeability coefficient across Caco-2 cells. The mechanism of transport was evaluated using phlorizin, an inhibitor of sodium-dependent glucose cotransporters (SGLT) 1 and 2, phloretin and quercetin, an inhibitors of glucose transporters (GLUT) 1 and 2, transcytosis inhibitor wortmannin, and gap junction disruptor cytochalasin D...
May 23, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28535208/sodium-glucose-cotransporter-2-in-mesangial-cells-and-retinal-pericytes-and-its-implications-for-diabetic-nephropathy-and-retinopathy
#2
Masarori Wakisaka, Tetsuhiko Nagao
Retinopathy and nephropathy are life-threatening diabetic complications that decrease patient quality of life. Although the mechanisms underlying these conditions have been extensively studied, they remain unknown. Recent reports have demonstrated the presence of SGLT2 in retinal pericytes and mesangial cells. Hyperglycemia results in functional and morphological changes in these cells, but these effects are attenuated by phlorizin, a non-selective SGLT inhibitor. Based on these findings, we hypothesized that SGLT2 plays a pivotal role in the development of diabetic nephropathy and retinopathy and that SGLT2 inhibitors may directly protect against these complications...
May 23, 2017: Glycobiology
https://www.readbyqxmd.com/read/28530382/diabetes-update-new-pharmacotherapy-for-type-2-diabetes
#3
Beth Choby
Multiple new drugs for managing type 2 diabetes have entered the market in the past 5 years. Guidelines from the American Diabetes Association recommend metformin for initial therapy, followed by a second drug if A1c goals are not met or initially for patients with A1c levels greater than 9%. Conversely, the American Association of Clinical Endocrinologists recommends initial management with two drugs if the A1c level is greater than 7.5%. The risk of lactic acidosis associated with metformin has been shown to be less than previously thought, with newer guidelines permitting use with an estimated glomerular filtration rate of 45 to 60 mL/min/1...
May 2017: FP Essentials
https://www.readbyqxmd.com/read/28526185/empa-reg-outcome-the-endocrinologist-s-point-of-view
#4
Leigh Perreault
For many years, it was widely accepted that control of plasma lipids and blood pressure could lower macrovascular risk in patients with type 2 diabetes mellitus (T2DM), whereas the benefits of lowering plasma glucose were largely limited to improvements in microvascular complications. The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) study demonstrated for the first time that a glucose-lowering agent, the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, could reduce major adverse cardiovascular events, cardiovascular mortality, hospitalization for heart failure, and overall mortality when given in addition to standard care in patients with T2DM at high cardiovascular risk...
May 12, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28526184/cardiovascular-protection-by-sodium-glucose-cotransporter-2-inhibitors-potential-mechanisms
#5
Bart Staels
The mechanism of action of empagliflozin in reducing the risk of adverse cardiovascular outcomes vs placebo in patients with type 2 diabetes mellitus and a high risk of cardiovascular disease in the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) trial is currently unknown. An antiatherosclerotic effect is considered unlikely given the speed of the observed decrease in cardiovascular mortality. Hemodynamic effects, such as reductions in blood pressure and intravascular volume, and involving osmotic diuresis, may provide a more plausible explanation...
May 15, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28526183/diabetes-mellitus-and-heart-failure
#6
Michael Lehrke, Nikolaus Marx
Epidemiologic and clinical data from the last 2 decades have shown that the prevalence of heart failure in diabetes is very high, and the prognosis for patients with heart failure is worse in those with diabetes than in those without diabetes. Experimental data suggest that various mechanisms contribute to the impairment in systolic and diastolic function in patients with diabetes, and there is an increased recognition that these patients develop heart failure independent of the presence of coronary artery disease or its associated risk factors...
May 15, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28526179/empa-reg-outcome-the-nephrologist-s-point-of-view
#7
Christoph Wanner
There is increasing evidence that sodium glucose cotransporter 2 (SGLT2) inhibitors have renoprotective effects, as demonstrated by the renal analyses from clinical trials including Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), CANagliflozin Treatment And Trial Analysis versus SUlphonylurea (CANTATA-SU), and the dapagliflozin renal study. The potential mechanisms responsible are likely multifactorial, and direct renovascular and hemodynamic effects are postulated to play a central role...
May 16, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28524098/sglt2-inhibitors-as-a-therapeutic-option-for-diabetic-nephropathy
#8
REVIEW
Daiji Kawanami, Keiichiro Matoba, Yusuke Takeda, Yosuke Nagai, Tomoyo Akamine, Tamotsu Yokota, Kazunori Sango, Kazunori Utsunomiya
Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) worldwide. Glycemic and blood pressure (BP) control are important but not sufficient to attenuate the incidence and progression of DN. Sodium-glucose cotransporter (SGLT) 2 inhibitors are a new class of glucose-lowering agent suggested to exert renoprotective effects in glucose lowering-dependent and independent fashions. Experimental studies have shown that SGLT2 inhibitors attenuate DN in animal models of both type 1 diabetes (T1D) and type 2 diabetes (T2D), indicating a potential renoprotective effect beyond glucose reduction...
May 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28523441/progress-in-the-presence-of-failure-updates-in-chronic-systolic-heart-failure-management
#9
REVIEW
Katie M Murphy, Julie L Rosenthal
The therapeutic heart failure armamentarium has evolved from drugs to transplantation to devices through further understanding of its complex pathophysiology and pathogenesis. Current medications capitalize on our evolving understanding of the sympathetic and renin-angiotensin-aldosterone systems that subsequently promote both beneficial and maladaptive responses that ultimately yield a decrease in cardiac function. Despite these advancements, the prevalence of heart failure continues to rise and carries a significant burden on our patients and health care system...
July 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28522675/effects-of-sodium-glucose-cotransporter-2-inhibitors-on-24-hour-ambulatory-blood-pressure-a-systematic-review-and-meta-analysis
#10
REVIEW
William L Baker, Leo F Buckley, Michael S Kelly, John D Bucheit, Eric D Parod, Roy Brown, Salvatore Carbone, Antonio Abbate, Dave L Dixon
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of antihyperglycemic agents that improve glycemic control by increasing glycosuria. Additional benefits beyond glucose lowering include significant improvements in seated clinic blood pressure (BP), partly attributed to their diuretic-like actions. Less known are the effects of this class on 24-hour ambulatory BP, which is a better predictor of cardiovascular risk than seated clinic BP. METHODS AND RESULTS: We performed a meta-analysis of randomized, double-blind, placebo-controlled trials to investigate the effects of SGLT2 inhibitors on 24-hour ambulatory BP...
May 18, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28522431/wnk1-and-p38-mapk-distribution-in-ionocytes-and-accessory-cells-of-euryhaline-teleost-fish-implies-ionoregulatory-function
#11
W S Marshall, R R F Cozzi, M Spieker
Ionocytes of euryhaline teleost fish secrete NaCl, under regulation by serine and threonine kinases, including with-no-lysine kinase (WNK1) and p38 mitogen-activated protein kinase (MAPK). Mummichogs (Fundulus heteroclitus L.) were acclimated to freshwater (FW), full strength seawater (SW) and hypersaline conditions (2SW). Immunocytochemistry of ionocytes in opercular epithelia of fish acclimated to SW and 2SW revealed that WNK1-anti-pT58 phosphoantibody localized strongly to accessory cells and was present in the cytosol of ionocytes close to, cystic fibrosis transmembrane conductance regulator (CFTR) in the apical membrane and sodium, potassium, 2 chloride cotransporter (NKCC) in basolateral membrane...
May 18, 2017: Biology Open
https://www.readbyqxmd.com/read/28517913/sodium-glucose-co-transporter-2-inhibitors-and-diabetic-ketoacidosis-an-updated-review-of-the-literature
#12
REVIEW
Benedetta Maria Bonora, Angelo Avogaro, Gian Paolo Fadini
AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are increasingly used for the treatment of type 2 diabetes (T2D) and can improve glucose control also in type 1 diabetes (T1D). In May 2015, regulatory agencies issued a warning that SGLT2i may cause diabetic ketoacidosis (DKA). We report details on two new cases of SGLT2i-associated DKA and review the literature for similar cases within randomised controlled trials (RCTs), cohort studies, and single reports. METHODS: We searched the medical literature for reports of SGLT2i-associated DKA cases...
May 18, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28511177/familial-hyperkalemia-and-hypertension-fhht-and-klhl3-description-of-a-family-with-a-new-recessive-mutation-s553l-compared-to-a-family-with-a-dominant-mutation-q309r-with-analysis-of-urinary-sodium-chloride-cotransporter
#13
Orit Kliuk-Ben Bassat, Vered Carmon, Aaron Hanukoglu, Liat Ganon, Eias Massalha, Eliezer J Holtzman, Zvi Farfel, Haim Mayan
BACKGROUND: Familial hyperkalemia and hypertension (FHHt) is an inherited disorder manifested by hyperkalemia and hypertension. The following four causative genes were identified: WNK1, WNK4, CUL3, and KLHL3. For the first 3 genes, inheritance is autosomal dominant. For KLHL3, inheritance is mostly dominant. A few cases with autosomal recessive disease were described. The mechanism of these 2 modes of inheritance is not clear. In the recessive form, the phenotype of heterozygotes is not well described...
May 17, 2017: Nephron
https://www.readbyqxmd.com/read/28507171/first-in-man-demonstration-of-direct-endothelin-mediated-natriuresis-and-diuresis
#14
Robert W Hunter, Rebecca Moorhouse, Tariq E Farrah, Iain M MacIntyre, Takae Asai, Peter J Gallacher, Debbie Kerr, Vanessa Melville, Alicja Czopek, Emma E Morrison, Jess R Ivy, James W Dear, Matthew A Bailey, Jane Goddard, David J Webb, Neeraj Dhaun
Endothelin (ET) receptor antagonists are potentially novel therapeutic agents in chronic kidney disease and resistant hypertension, but their use is complicated by sodium and water retention. In animal studies, this side effect arises from ETB receptor blockade in the renal tubule. Previous attempts to determine whether this mechanism operates in humans have been confounded by the hemodynamic consequences of ET receptor stimulation/blockade. We aimed to determine the effects of ET signaling on salt transport in the human nephron by administering subpressor doses of the ET-1 precursor, big ET-1...
May 15, 2017: Hypertension
https://www.readbyqxmd.com/read/28506912/characterization-and-comparison-of-sglt2-inhibitors-part-3-effects-on-diabetic-complications-in-type-2-diabetic-mice
#15
Atsuo Tahara, Toshiyuki Takasu, Masanori Yokono, Masakazu Imamura, Eiji Kurosaki
In this study, we investigated and compared the effects of all six sodium-glucose cotransporter (SGLT) 2 inhibitors commercially available in Japan on diabetes-related diseases and complications in type 2 diabetic mice. Following 4-week repeated administration to diabetic mice, all SGLT2 inhibitors showed significant improvement in diabetes-related diseases and complications, including obesity; abnormal lipid metabolism; steatohepatitis; inflammation; endothelial dysfunction; and nephropathy. While all SGLT2 inhibitors exerted comparable effects in reducing hyperglycemia, improvement of these diabetes-related diseases and complications was more potent with the two long-acting drugs (ipragliflozin and dapagliflozin) than with the four intermediate-acting four drugs (tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin), albeit without statistical significance...
May 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28506519/sodium-glucose-co-transporters-and-their-inhibition-clinical-physiology
#16
REVIEW
Ele Ferrannini
Sodium-glucose cotransporter-2 (SGLT2) is selectively expressed in the human kidney, where it executes reabsorption of filtered glucose with a high capacity; it may be overactive in patients with diabetes, especially in the early, hyperfiltering stage of the disease. As a therapeutic target, SGLT2 has been successfully engaged by orally active, selective agents. Initially developed as antihyperglycemic drugs, SGLT2 inhibitors have deployed a range of in vivo actions. Consequences of their primary effect, i...
May 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28504650/neutrophil-derived-s100-calcium-binding-proteins-a8-a9-promote-reticulated-thrombocytosis-and-atherogenesis-in-diabetes
#17
Michael J Kraakman, Man K S Lee, Annas Al-Sharea, Dragana Dragoljevic, Tessa J Barrett, Emilie Montenont, Debapriya Basu, Sarah Heywood, Helene L Kammoun, Michelle Flynn, Alexandra Whillas, Nordin M J Hanssen, Mark A Febbraio, Erik Westein, Edward A Fisher, Jaye Chin-Dusting, Mark E Cooper, Jeffrey S Berger, Ira J Goldberg, Prabhakara R Nagareddy, Andrew J Murphy
Platelets play a critical role in atherogenesis and thrombosis-mediated myocardial ischemia, processes that are accelerated in diabetes. Whether hyperglycemia promotes platelet production and whether enhanced platelet production contributes to enhanced atherothrombosis remains unknown. Here we found that in response to hyperglycemia, neutrophil-derived S100 calcium-binding proteins A8/A9 (S100A8/A9) interact with the receptor for advanced glycation end products (RAGE) on hepatic Kupffer cells, resulting in increased production of IL-6, a pleiotropic cytokine that is implicated in inflammatory thrombocytosis...
May 15, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28502502/dapagliflozin-in-patients-with-type-ii-diabetes-mellitus-with-and-without-elevated-triglyceride-and-reduced-high-density-lipoprotein-cholesterol-levels
#18
Harold E Bays, Peter Sartipy, John Xu, Carl David Sjöström, James A Underberg
BACKGROUND: Dapagliflozin is a selective sodium-glucose cotransporter 2 inhibitor that improves glycemic control in patients with type II diabetes mellitus (T2DM) by reducing renal glucose reabsorption. OBJECTIVE: The aim was to evaluate the lipid effects of dapagliflozin 10 mg or placebo in patients with T2DM with/without baseline elevated triglyceride and reduced high-density lipoprotein (HDL) cholesterol levels. METHODS: This was a post hoc analysis of 10 phase 3, placebo-controlled studies of dapagliflozin 10 mg (N = 2237) or placebo (N = 2164) administered for 24 weeks in patients with T2DM...
March 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28501906/medication-use-for-the-treatment-of-diabetes-in-obese-individuals
#19
REVIEW
John P H Wilding
Obesity is a major cause of type 2 diabetes and may complicate type 1 diabetes. Weight loss for obese individuals with diabetes has many health benefits, often leads to improvement in glucose control and sometimes, in type 2 diabetes, near normalisation of abnormal glucose metabolism. Weight loss is difficult to maintain and attempts to lose weight may be undermined by some diabetes treatments such as sulfonylureas, thiazolidinediones and insulin. Whilst lifestyle support should be the primary approach to aid individuals who wish to lose weight, pharmacological approaches can also be considered...
May 14, 2017: Diabetologia
https://www.readbyqxmd.com/read/28496544/hemodynamic-effects-of-sodium-glucose-cotransporter-2-inhibitors
#20
REVIEW
Motoaki Sano
It is widely accepted that obesity and type 2 diabetes mellitus (T2DM) increase the risk of heart failure (HF) independently of underlying coronary artery disease. The changes in myocardial structure or function associated with diabetes have been termed diabetic cardiomyopathy. Corresponding to changes in the risk factors for HF, an epidemiologic transition is underway from HF with a reduced ejection fraction to HF with a preserved ejection fraction. Hyperglycemia can damage the myocardium, even before diagnosis of diabetes, but intensive glycemic control has no impact on the risk of HF in patients with T2DM...
June 2017: Journal of Clinical Medicine Research
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