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Sodium cotransporter

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https://www.readbyqxmd.com/read/29779957/de-novo-macrocyclic-peptide-inhibitors-of-hepatitis-b-virus-cellular-entry
#1
Toby Passioura, Koichi Watashi, Kento Fukano, Satomi Shimura, Wakana Saso, Ryo Morishita, Yuki Ogasawara, Yasuhito Tanaka, Masashi Mizokami, Camille Sureau, Hiroaki Suga, Takaji Wakita
Hepatitis B virus (HBV) constitutes a significant public health burden, and currently available treatment options are not generally curative, necessitating the development of new therapeutics. Here we have applied random non-standard peptide integrated discovery (RaPID) screening to identify small macrocyclic peptide inhibitors of HBV entry that target the cell-surface receptor for HBV, sodium taurocholate cotransporting polypeptide (NTCP). In addition to their anti-HBV activity, these molecules also inhibit cellular entry by the related hepatitis D virus (HDV), and are active against diverse strains of HBV (including clinically relevant nucleos(t)ide analog-resistant and vaccine escaping strains)...
May 2, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29777264/empagliflozin-reduces-cardiovascular-events-mortality-and-renal-events-in-participants-with-type-2-diabetes-after-coronary-artery-bypass-graft-surgery-subanalysis-of-the-empa-reg-outcome%C3%A2-randomised-trial
#2
Subodh Verma, C David Mazer, David Fitchett, Silvio E Inzucchi, Egon Pfarr, Jyothis T George, Bernard Zinman
AIMS/HYPOTHESIS: After coronary artery bypass graft (CABG) surgery in individuals with type 2 diabetes, there remains a considerable residual cardiovascular risk. In the EMPA-REG OUTCOME® trial in participants with type 2 diabetes and established cardiovascular disease, empagliflozin reduced the risk of cardiovascular death by 38%, all-cause mortality by 32%, hospitalisation for heart failure by 35% and incident or worsening nephropathy by 39% vs placebo when given in addition to standard of care...
May 19, 2018: Diabetologia
https://www.readbyqxmd.com/read/29767556/hydronephrosis-is-associated-with-elevated-plasmin-in-urine-in-pediatric-patients-and-rats-and-changes-in-ncc-and-%C3%AE-enac-abundance-in-rat-kidney
#3
Rikke Zachar, Ammar Al-Mashhadi, Henrik Dimke, Per Svenningsen, Boye L Jensen, Mattias Carlström
Obstruction of urine flow at the level of the pelvo-ureteric junction (UPJO) and subsequent development of hydronephrosis is one of the most common congenital renal malformations. UPJO is associated with development of salt-sensitive hypertension, which is set by the obstructed kidney, and with a stimulated renin-angiotensin-aldosterone system (RAAS) in rodent models. This study aimed at investigating the hypothesis that i) in pediatric patients with UPJO the RAAS is activated prior to surgical relief of the obstruction; ii) in rats with UPJO the RAAS activation is reflected by increased abundance of renal aldosterone-stimulated Na+ transporters; and iii) the injured UPJO kidney allows aberrant filtration of plasminogen leading to proteolytic activation of the epithelial sodium channel gamma subunit (γ-ENaC)...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29766812/switching-dipeptidyl-peptidase-4-inhibitors-to-tofogliflozin-a-selective-inhibitor-of-sodium-glucose-cotransporter-2-improves-arterial-stiffness-evaluated-by-cardio-ankle-vascular-index-in-patients-with-type-2-diabetes
#4
Nobuhiro Tahara, Sho-Ichi Yamagish, Munehisa Bekki, Atsuko Tahara, Sachiyo Igata, Akihiro Honda, Yoichi Sugiyama, Tomohisa Nakamura, Jiahui Sun, Yuki Kumashiro, Takanori Matsui, Yoshihiro Fukumoto
BACKGROUND: We have found that anagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4) significantly ameliorates arterial stiffness in type 2 diabetes mellitus (T2DM) patients compared with an equivalent hypoglycemic agent, glimepiride. However, it remains unclear whether and how switching DPP-4 inhibitors to tofogliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2) improves arterial stiffness in T2DM patients. METHODS: Nineteen T2DM patients who had received DPP-4 inhibitors for at least 1 year were enrolled in this study...
May 15, 2018: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29751356/exploring-novel-pharmacotherapeutic-applications-and-repurposing-potential-of-sodium-glucose-cotransporter-2-sglt2-inhibitors
#5
REVIEW
Tushar Madaan, Ibraheem Husain, Mohamad Akhtar, Abul Kalam Najmi
Sodium glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of anti-hyperglycemic drugs with a distinctive mechanism of action focusing on renal absorption ofglucose. Apart from its anti-hyperglycemic effects, a multitude of research studies on this classhave revealed that these drugs have far more versatile and comprehensive pharmacologicaleffects than previously believed. Approximately 30% of FDA approved drugs are repurposedand used for indications other than those they were initially intended for...
May 11, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29748368/cardiovascular-effects-of-new-oral-glucose-lowering-agents-dpp-4-and-sglt-2-inhibitors
#6
REVIEW
André J Scheen
Cardiovascular disease (CVD) is a major challenge in the management of type 2 diabetes mellitus. Glucose-lowering agents that reduce the risk of major cardiovascular events would be considered a major advance, as recently reported with liraglutide and semaglutide, 2 glucagon-like peptide-1 receptor agonists, and with empagliflozin and canagliflozin, 2 SGLT-2 (sodium-glucose cotransporter type 2) inhibitors, but not with DPP-4 (dipeptidyl peptidase-4) inhibitors. The present review is devoted to CV effects of new oral glucose-lowering agents...
May 11, 2018: Circulation Research
https://www.readbyqxmd.com/read/29747423/use-of-diabetes-treatment-satisfaction-questionnaire-in-diabetes-care-importance-of-patient-reported-outcomes
#7
REVIEW
Yoshifumi Saisho
The efficacy of diabetes treatment should not be evaluated solely by HbA1c levels as they should also focus on patient-reported outcomes (PROs), such as patient satisfaction, wellbeing and quality of life. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) has been developed to assess patient satisfaction with diabetes treatment. DTSQ has been translated into more than 100 languages and is widely used in many countries, since it is relatively easy to answer and is used for both patients with and without medical therapy...
May 9, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29747077/asemeia-ovata-polygalaceae-quantitative-determination-and-evaluation-in-silico-of-identified-substances-by-hplc-dad
#8
José Luiz Carneiro da Rocha, Danielle Figuerêdo da Silva, Anne Ramos de Santana, Diego Mota da Costa, José Floriano Barêa Pastore, Clayton Queiroz Alves, Manoelito Coelho Santos Santos Junior, Hugo Neves Brandão
BACKGROUND: In Brazil, the Asemeia genus has 19 species (12 endemic) and 2 varieties (both endemic) and some of them are found in semi-arid Bahia. OBJECTIVE: The objective of this study was to quantitatively determine identified substances by HPLC-DAD in Asemeia ovata extracts and to predict their biological activities in silico. METHOD: The quantification method by HPLC-DAD has been validated according to the guidelines of the International Conference of Harmonization...
April 30, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29736951/factors-associated-with-advanced-hepatic-fibrosis-in-patients-with-various-internal-diseases-a-multicenter-community-based-survey
#9
Takumi Kawaguchi, Tetsuaki Inokuchi, Tomoki Honma, Satoshi Itano, Eiji Kawasaki, Chizuko Inada, Toshichika Aoki, Naohira Tsumura, Akiteru Araki, Tokunori Mukae, Takuji Torimura
BACKGROUND AND AIMS: Advanced hepatic fibrosis can occur in patients with various diseases, including diabetes mellitus and hypertension. We aimed to investigate the prevalence and risk factors of advanced hepatic fibrosis in patients with various internal diseases. PATIENTS AND METHODS: We performed a community-based survey in which 1,012 patients were enrolled (mean age, 63.1 ± 10.8 years; female/male, 505/507). Hepatic fibrosis was evaluated by Fib-4 index and patients were classified into high and low Fib-4 groups...
May 7, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29735631/renal-specific-silencing-of-tnf-tumor-necrosis-factor-unmasks-salt-dependent-increases-in-blood-pressure-via-an-nkcc2a-na-k-2cl-cotransporter-isoform-a-dependent-mechanism
#10
Shoujin Hao, Mary Hao, Nicholas R Ferreri
We tested the hypothesis that TNF (tumor necrosis factor)-α produced within the kidney and acting on the renal tubular system is part of a regulatory mechanism that attenuates increases in blood pressure in response to high salt intake. Intrarenal administration of a lentivirus construct, which specifically silenced TNF in the kidney, did not affect baseline blood pressure. However, blood pressure increased significantly 1 day after mice with intrarenal silencing of TNF ingested 1% NaCl in the drinking water...
May 7, 2018: Hypertension
https://www.readbyqxmd.com/read/29735306/renoprotective-effects-of-sodium-glucose-cotransporter-2-inhibitors
#11
REVIEW
Hiddo J L Heerspink, Mikhail Kosiborod, Silvio E Inzucchi, David Z I Cherney
Over the past two years, our understanding of anti-hyperglycemic medications used to treat patients with type 2 diabetes (T2D) has fundamentally changed. Before the EMPA-REG OUTCOME trial, agents used to lower blood glucose were felt to prevent or delay the development of microvascular complications, but were not known to definitively reduce cardiovascular risk or mortality. Previous studies with then novel sodium-glucose cotransport-2 (SGLT2) inhibitors demonstrated improvements in several cardiovascular and renal risk factors, including HbA1c, blood pressure, weight, renal hyperfiltration, and albuminuria...
May 5, 2018: Kidney International
https://www.readbyqxmd.com/read/29730285/a-new-strategy-to-identify-hepatitis-b-virus-entry-inhibitors-by-alphascreen-technology-targeting-the-envelope-receptor-interaction
#12
Wakana Saso, Senko Tsukuda, Hirofumi Ohashi, Kento Fukano, Ryo Morishita, Satoko Matsunaga, Mio Ohki, Akihide Ryo, Sam-Yong Park, Ryosuke Suzuki, Hideki Aizaki, Masamichi Muramatsu, Camille Sureau, Takaji Wakita, Tetsuro Matano, Koichi Watashi
Current anti-hepatitis B virus (HBV) agents have limited effect in curing HBV infection, and thus novel anti-HBV agents with different modes of action are in demand. In this study, we applied AlphaScreen assay to high-throughput screening of small molecules inhibiting the interaction between HBV large surface antigen (LHBs) and the HBV entry receptor, sodium taurocholate cotransporting polypeptide (NTCP). From the chemical screening, we identified that rapamycin, an immunosuppressant, strongly inhibited the LHBs-NTCP interaction...
May 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29726949/increased-urinary-extracellular-vesicle-sodium-transporters-in-cushing-s-syndrome-with-hypertension
#13
Mahdi Salih, Dominique M Bovée, Nils van der Lubbe, Alexander H J Danser, Robert Zietse, Richard A Feelders, Ewout J Hoorn
Context: Increased renal sodium reabsorption contributes to hypertension in Cushing's syndrome (CS). Renal sodium transporters can be analyzed non-invasively in urinary extracellular vesicles (uEVs). Objective: To analyze renal sodium transporters in uEVs of patients with CS and hypertension. Design: Observational study. Setting: University hospital. Participants: uEVs were isolated by ultracentrifugation and analyzed by immunoblotting in 10 CS patients and 7 age-matched healthy subjects...
May 2, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29723527/inhibitory-effect-of-fasiglifam-on-hepatitis-b-virus-infections-through-suppression-of-the-sodium-taurocholate-cotransporting-polypeptide
#14
Yasunori Nio, Yuichi Akahori, Hitomi Okamura, Koichi Watashi, Takaji Wakita, Makoto Hijikata
Fasiglifam is a selective partial agonist of G-protein-coupled receptor 40 (GPR40), which was developed for the treatment of type 2 diabetes mellitus. However, the clinical development of fasiglifam was voluntarily terminated during phase III clinical trials due to adverse liver effects. Fasiglifam showed an inhibitory effect on sodium taurocholate cotransporting polypeptide (NTCP) in human and rat hepatocytes. Recently, NTCP was reported to be a functional receptor for human hepatitis B virus (HBV) infections...
April 30, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29717223/effect-of-the-sodium-glucose-cotransporter-2-inhibitor-luseogliflozin-on-pancreatic-beta-cell-mass-in-db-db-mice-of-different-ages
#15
Kiyohiko Takahashi, Akinobu Nakamura, Hideaki Miyoshi, Hiroshi Nomoto, Naoyuki Kitao, Kazuno Omori, Kohei Yamamoto, Kyu Yong Cho, Yasuo Terauchi, Tatsuya Atsumi
To examine the effects of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, on pancreatic beta cell mass in db/db mice of different ages. db/db mice aged 6, 10, 14 and 24 weeks old were fed either standard chow (control group) or standard chow containing 0.01% luseogliflozin (luseo group). After 4 weeks, immunohistochemistry and gene expression tests were conducted. In 6-week-old db/db mice, immunohistochemistry revealed a significant increase in beta cell mass in the luseo group compared with the control group after 4 weeks of treatment...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29717156/high-basolateral-glucose-increases-sodium-glucose-cotransporter-2-and-reduces-sirtuin-1-in-renal-tubules-through-glucose-transporter-2-detection
#16
Hiroyuki Umino, Kazuhiro Hasegawa, Hitoshi Minakuchi, Hirokazu Muraoka, Takahisa Kawaguchi, Takeshi Kanda, Hirobumi Tokuyama, Shu Wakino, Hiroshi Itoh
Under diabetic conditions, sodium-glucose cotransporter 2 (SGLT2) for glucose uptake in proximal tubules (PTs) increases, whereas NAD+ -dependent protein deacetylase silent mating type information regulation 2 homolog 1 (Sirtuin-1; SIRT1) for PT survival decreases. Therefore, we hypothesized that increased glucose influx by SGLT2 reduces SIRT1 expression. To test this hypothesis, db/db mice with diabetes and high-glucose (HG)-cultured porcine PT LLC-PK1 cells in a two-chamber system were treated with the SGLT2 inhibitor canagliflozin...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29709913/protective-effect-of-ipragliflozin-on-pancreatic-islet-cells-in-obese-type-2-diabetic-db-db-mice
#17
Toshiyuki Takasu, Shoji Takakura
Ipragliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that increases urinary glucose excretion and subsequently improves hyperglycemia in patients with type 2 diabetes mellitus (T2DM). To assess the beneficial effect of ipragliflozin on the mass and function of pancreatic β-cells under diabetic conditions, obese T2DM db/db mice were treated with ipragliflozin for 5 weeks. Glucose and lipid metabolism parameters, pathological changes in pancreatic islet cells and insulin content were evaluated...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29707805/intestinal-absorption-of-glucose-in-mice-as-determined-by-positron-emission-tomography
#18
Monica Sala-Rabanal, Chiara Ghezzi, Bruce A Hirayama, Vladimir Kepe, Jie Liu, Jorge R Barrio, Ernest M Wright
KEY POINTS: The goal was to determine the importance of the sodium glucose cotransporter SGLT1 and the glucose uniporter GLUT2 in intestinal glucose absorption during oral glucose tolerance tests (OGTTs) in mice. Glucose absorption was determined in mice using positron emission tomography and three non-metabolizable glucose probes: one specific for SGLTs, one specific for GLUTs, and one a substrate for both SGLTs and GLUTs. Absorption was determined in wild-type, Sglt1-/- , and Glut2-/- mice...
April 29, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29707091/sodium-glucose-cotransporter-2-inhibitors-reduce-prandial-insulin-doses-in-type-2-diabetic-patients-treated-with-the-intensive-insulin-therapy
#19
Mariko Hakoshima, Hidekatsu Yanai, Kouki Kakuta, Hiroki Adachi
Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are anti-diabetic drugs which improve blood glucose control by blocking reabsorption of glucose from the proximal tubule of kidney. Anti-atherosclerotic properties and cardiovascular protective effects of SGLT2i have been demonstrated by recent studies; however, the efficacy and safety of addition of SGLT2i to the intensive insulin therapy remain largely unknown. Methods: We retrospectively picked up patients hospitalized for treatment of type 2 diabetes, who had been treated by the intensive insulin therapy and whose treatment using by SGLT2i started during their hospitalization...
June 2018: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/29707088/impact-of-dapagliflozin-therapy-on-renal-protection-and-kidney-morphology-in-patients-with-uncontrolled-type-2-diabetes-mellitus
#20
Seigo Sugiyama, Hideaki Jinnouchi, Noboru Kurinami, Kunio Hieshima, Akira Yoshida, Katsunori Jinnouchi, Motoko Tanaka, Hiroyuki Nishimura, Tomoko Suzuki, Fumio Miyamoto, Keizo Kajiwara, Tomio Jinnouchi
Background: We examined whether the sodium-glucose cotransporter-2 inhibitor (SGLT2i) dapagliflozin can improve urine albumin-to-creatinine ratio (UACR) associated with a reduction in body weight or body fat in patients with type 2 diabetes mellitus (T2DM). Methods: We prospectively recruited T2DM patients having inadequate glycemic control (hemoglobin A1c (HbA1c) > 7.0%) not on SGLT2i therapy. We treated the patients with add-on dapagliflozin treatment or intensification of non-SGLT2 inhibitor therapies for 6 months...
June 2018: Journal of Clinical Medicine Research
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