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Sodium cotransporter

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https://www.readbyqxmd.com/read/28646412/efficacy-of-additional-canagliflozin-administration-to-type-2-diabetes-patients-receiving-insulin-therapy-examination-of-diurnal-glycemic-patterns-using-continuous-glucose-monitoring-cgm
#1
Mihoko Matsumura, Yuki Nakatani, Seiichi Tanka, Chie Aoki, Masaaki Sagara, Kazunori Yanagi, Kunihiro Suzuki, Yoshimasa Aso
INTRODUCTION: The efficacy of administering a sodium-glucose cotransporter 2 inhibitor during insulin therapy has not been established. In this study, we examined its effects based on diurnal glycemic patterns using continuous glucose monitoring (CGM). METHODS: The subjects were 15 patients who had received insulin therapy for 1 year or more. A CGM device was attached to all subjects for 1 week. The administration of canagliflozin at 100 mg was started 4 days after attachment...
June 23, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28646163/aldosterone-modulates-the-association-between-ncc-and-enac
#2
Brandi M Wynne, Abinash C Mistry, Otor Al-Khalili, Rickta Mallick, Franziska Theilig, Douglas C Eaton, Robert S Hoover
Distal sodium transport is a final step in the regulation of blood pressure. As such, understanding how the two main sodium transport proteins, the thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC), are regulated is paramount. Both are expressed in the late distal nephron; however, no evidence has suggested that these two sodium transport proteins interact. Recently, we established that these two sodium transport proteins functionally interact in the second part of the distal nephron (DCT2)...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28643218/empagliflozin-improves-left-ventricular-diastolic-dysfunction-in-a-genetic-model-of-type-2-diabetes
#3
Nadjib Hammoudi, Dongtak Jeong, Rajvir Singh, Ahmed Farhat, Michel Komajda, Eric Mayoux, Roger Hajjar, Djamel Lebeche
PURPOSE: Cardiovascular (CV) diseases in type 2 diabetes (T2DM) represent an enormous burden with high mortality and morbidity. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently emerged as a new antidiabetic class that improves glucose control, as well as body weight and blood pressure with no increased risk of hypoglycemia. The first CV outcome study terminated with empagliflozin, a specific SGLT2 inhibitor, has shown a reduction in CV mortality and in heart failure hospitalization, suggesting a beneficial impact on cardiac function which remains to be demonstrated...
June 22, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28641949/reduced-protein-expressions-of-cytomembrane-gabaar%C3%AE-3-at-different-postnatal-developmental-stages-of-rats-exposed-prenatally-to-valproic-acid
#4
Yixin Li, Yang Zhou, Li Peng, Yong Zhao
Decreased inhibition plays an extremely important role in pathogenesis of autism spectrum disorder (ASD). Therefore, we aimed to determine whether expression levels of the γ-aminobutyric acid type A receptor β3 subunit (GABAARβ3), K(+)-Cl(-) cotransporter 2 (KCC2), and Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) related to inhibition transmission are changed in a sodium valproate-induced rat model of ASD. Decreased expression levels of membrane GABAARβ3 (m-GABAARβ3) and KCC2 as well as increased endocytosis of GABAARs were found in the model group...
June 19, 2017: Brain Research
https://www.readbyqxmd.com/read/28639760/-euglycemic-ketoacidosis-a-complication-of-sglt2-inhibitors
#5
Aki Mizuno, Sanaz Lolachi, Alain Pernet
Sodium-glucose cotransporter 2 (SGLT2) inhibitors constitute a new category of oral antidiabetics recently indicated for the treatment of type 2 diabetes. Their mechanism of action (inhibition of renal reabsorption of glucose) and the fact that they do not induce hypoglycemia (as monotherapy) make their clinical use interesting. Various adverse events have however been reported regarding these drugs with the euglycemic ketoacidosis being the most serious. In this article we aim to review the possible mechanism of this side effect and recommendations for use of SGLT2 inhibitors by means of a case report...
May 31, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28637887/mitigating-cardiovascular-risk-in-type-2-diabetes-with-antidiabetes-drugs-a-review-of-principal-cardiovascular-outcome-results-of-empa-reg-outcome-leader-and-sustain-6-trials
#6
Sanjay Kaul
The U.S. Food and Drug Administration (FDA) issued a diabetes guidance in 2008 mandating that all new antidiabetes drugs rule out excess cardiovascular (CV) risk, defined as an upper bound of the two-sided 95% CI for major adverse CV events (MACE) of less than 1.80 preapproval and 1.30 postapproval. Over 25 large, prospective, randomized, controlled clinical trials involving nearly 195,000 subjects thus far have been completed or are ongoing in accordance with this guidance. The results of seven trials have been presented so far-three with dipeptidyl peptidase 4 inhibitors, one with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and three with glucagon-like peptide 1 receptor agonists (GLP-1 RA)...
July 2017: Diabetes Care
https://www.readbyqxmd.com/read/28636701/the-metabolodiuretic-promise-of-sodium-dependent-glucose-cotransporter-2-inhibition-the-search-for-the-sweet-spot-in-heart-failure
#7
Subodh Verma, John J V McMurray, David Z I Cherney
No abstract text is available yet for this article.
June 21, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28635308/combined-hqsar-topomer-comfa-homology-modeling-and-docking-studies-on-triazole-derivatives-as-sglt2-inhibitors
#8
Shuling Yu, Jintao Yuan, Yi Zhang, Shufang Gao, Ying Gan, Meng Han, Yuewen Chen, Qiaoqiao Zhou, Jiahua Shi
AIM: Sodium-glucose cotransporter 2 (SGLT2) is a promising target for diabetes therapy. We aimed to develop computational approaches to identify structural features for more potential SGLT2 inhibitors. MATERIALS & METHODS: In this work, 46 triazole derivatives as SGLT2 inhibitors were studied using a combination of several approaches, including hologram quantitative structure-activity relationships (HQSAR), topomer comparative molecular field analysis (CoMFA), homology modeling, and molecular docking...
June 21, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28634592/euglycemic-diabetic-ketoacidosis-with-prolonged-glucosuria-associated-with-the-sodium-glucose-cotransporter-2-canagliflozin
#9
Daniel A Kelmenson, Kelsey Burr, Yusra Azhar, Paul Reynolds, Chelsea A Baker, Neda Rasouli
Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve glycemic control by a reversible inhibition of the sodium-glucose cotransporters in the renal proximal tubules resulting in increased urinary glucose. This unique mechanism, independent of insulin secretion and beta cell function, has made this class of medication desirable in patients with type 2 diabetes. However in May 2015, the US Food and Drug Administration issued a safety warning pertaining to the development of diabetic ketoacidosis (DKA) with the use of SGLT2 inhibitors...
April 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28631762/-safety-and-tolerability-of-oral-hypoglycemic-therapies-in-type-2-diabetes-mellitus-patients-at-high-cardiovascular-risk
#10
Giuseppe Ambrosio, Gaetano M De Ferrari, Massimo Federici, Pasquale Perrone Filardi
Oral hypoglycemic drugs for type 2 diabetes aim at preventing the metabolic effects of hyperglycemia and cardiovascular (CV) events. The evidence of the possible CV risk related to the prescription of some antidiabetic drugs prompted regulatory agencies to require safety studies. This review provides an updated analysis of CV safety profiles for antidiabetic drugs used for the treatment of patients with high CV risk.The most recent studies analyze different aspects of CV morbidity, such as ischemic events, heart failure and arrhythmia, and their interactions with hyperglycemia...
June 2017: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28630133/dual-regulation-of-gluconeogenesis-by-insulin-and-glucose-in-the-proximal-tubules-of-the-kidney
#11
Motohiro Sasaki, Takayoshi Sasako, Naoto Kubota, Yoshitaka Sakurai, Iseki Takamoto, Tetsuya Kubota, Reiko Inagi, George Seki, Moritaka Goto, Kohjiro Ueki, Masaomi Nangaku, Takahito Jomori, Takashi Kadowaki
Growing attention has been focused on the roles of the proximal tubules (PTs) of the kidney in glucose metabolism, including the mechanism of regulation of gluconeogenesis. Here, we found that PT-specific IRS1/2 double-knockout mice, established by using the newly generated sodium-glucose cotransporter-2 (SGLT2)-Cre transgenic mice, exhibited impaired insulin signaling and upregulated gluconeogenic gene expression and renal gluconeogenesis, resulting in systemic insulin resistance. On the other hand, in streptozotocin-treated mice, although insulin action was impaired in the PTs, the gluconeogenic gene expression was unexpectedly downregulated in the renal cortex, which was restored by administration of an SGLT1/2 inhibitor...
June 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28624460/identification-of-kx2-391-as-an-inhibitor-of-hbv-transcription-by-a-recombinant-hbv-based-screening-assay
#12
Keisuke Harada, Hironori Nishitsuji, Saneyuki Ujino, Kunitada Shimotohno
Antiviral therapies for chronic hepatitis B virus (HBV) infection that are currently applicable for clinical use are limited to nucleos(t)ide analogs targeting HBV polymerase activity and pegylated interferon alpha (PEG-IFN). Towards establishing an effective therapy for HBV related diseases, it is important to develop a new anti-HBV agent that suppresses and eradicates HBV. This study used recombinant HBV encoding NanoLuc to screen anti-HBV compounds from 1827 US Food and Drug Administration approved compounds and identified several compounds that suppressed HBV infection...
June 15, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28619994/simultaneous-stimulation-of-glycolysis-and-gluconeogenesis-by-feeding-in-the-anterior-intestine-of-the-omnivorous-gift-tilapia-oreochromis-niloticus
#13
Yong-Jun Chen, Ti-Yin Zhang, Hai-Yan Chen, Shi-Mei Lin, Li Luo, De-Shou Wang
The present study was performed to investigate the roles of anterior intestine in the postprandial glucose homeostasis of the omnivorous Genetically Improved Farmed Tilapia (GIFT). Sub-adult fish (about 173 g) were sampled at 0, 1, 3, 8 and 24 h post feeding (HPF) after 36 h of food deprivation, and the time course of changes in intestinal glucose transport, glycolysis, glycogenesis and gluconeogenesis at the transcription and enzyme activity level, as well as plasma glucose contents, were analyzed. Compared with 0 HPF (fasting for 36 h), the mRNA levels of both ATP-dependent sodium/glucose cotransporter 1 and facilitated glucose transporter 2 increased during 1-3 HPF, decreased at 8 HPF and then leveled off...
June 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28611861/effects-of-six-kinds-of-sodium-glucose-cotransporter-2-inhibitors-on-metabolic-parameters-and-summarized-effect-and-its-correlations-with-baseline-data
#14
Hidekatsu Yanai, Mariko Hakoshima, Hiroki Adachi, Akiko Kawaguchi, Yoko Waragai, Tadanao Harigae, Yoshinori Masui, Kouki Kakuta, Hidetaka Hamasaki, Hisayuki Katsuyama, Tomoko Kaga, Akahito Sako
BACKGROUND: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) blocks reabsorption of glucose by inhibiting SGLT2 in kidney, promotes the renal excretion of glucose and improves blood glucose control without requiring insulin secretion. Anti-atherosclerotic effects of SGLT2is have not been fully elucidated until today. METHODS: We retrospectively picked up patients with type 2 diabetes who had been continuously prescribed SGLT2i for 3 months or more between April 2014 and December 2016 by a chart-based analysis, and compared metabolic parameters including coronary risk factors before the SGLT2i treatment with the data at 3 and 6 months after the SGLT2i treatment started...
July 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28606346/empa-reg-outcome-the-nephrologist-s-point-of-view
#15
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...
July 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28606344/empa-reg-outcome-the-endocrinologist-s-point-of-view
#16
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...
July 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28606342/diabetes-mellitus-and-heart-failure
#17
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...
July 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28606341/cardiovascular-protection-by-sodium-glucose-cotransporter-2-inhibitors-potential-mechanisms
#18
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...
July 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28605608/canagliflozin-and-cardiovascular-and-renal-events-in-type-2-diabetes
#19
Bruce Neal, Vlado Perkovic, Kenneth W Mahaffey, Dick de Zeeuw, Greg Fulcher, Ngozi Erondu, Wayne Shaw, Gordon Law, Mehul Desai, David R Matthews
Background Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188...
June 12, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28598954/role-of-the-sympathetic-nervous-system-in-regulation-of-the-sodium-glucose-cotransporter-2
#20
Vance B Matthews, Rosemary H Elliot, Caroline Rudnicka, Jana Hricova, Lakshini Herat, Markus P Schlaich
BACKGROUND: The sympathetic nervous system (SNS) regulates glucose metabolism in various organs including the kidneys. The sodium glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in renal proximal tubules and its inhibition has been shown to improve glucose control, cardiovascular and renal outcomes. We hypothesized that SNS-induced alterations of glucose metabolism may be mediated via regulation of SGLT2. METHOD: We used human renal proximal tubule cells to investigate the effects of noradrenaline on SGLT2 regulation...
June 8, 2017: Journal of Hypertension
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