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Sodium cotransporter

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https://www.readbyqxmd.com/read/28938561/preventive-effects-of-the-sodium-glucose-cotransporter-2-inhibitor-tofogliflozin-on-diethylnitrosamine-induced-liver-tumorigenesis-in-obese-and-diabetic-mice
#1
Koki Obara, Yohei Shirakami, Akinori Maruta, Takayasu Ideta, Tsuneyuki Miyazaki, Takahiro Kochi, Hiroyasu Sakai, Takuji Tanaka, Mitsuru Seishima, Masahito Shimizu
Sodium glucose cotransporter 2 inhibitors are expected to ameliorate the abnormalities associated with metabolic syndrome including non-alcoholic fatty liver disease. In this study, we investigated the effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on the development of non-alcoholic fatty liver disease-related liver tumorigenesis in C57BL/KsJ-+Lepr (db) /+Lepr (db) obese and diabetic mice. The direct effects of tofogliflozin on human liver cancer cell proliferation were also evaluated...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28935959/the-crystal-structure-of-the-regulatory-domain-of-the-human-sodium-driven-chloride-bicarbonate-exchanger
#2
Carolina M Alvadia, Theis Sommer, Kaare Bjerregaard-Andersen, Helle Hasager Damkier, Michele Montrasio, Christian Aalkjaer, J Preben Morth
The sodium-driven chloride/bicarbonate exchanger (NDCBE) is essential for maintaining homeostatic pH in neurons. The crystal structure at 2.8 Å resolution of the regulatory N-terminal domain of human NDCBE represents the first crystal structure of an electroneutral sodium-bicarbonate cotransporter. The crystal structure forms an equivalent dimeric interface as observed for the cytoplasmic domain of Band 3, and thus establishes that the consensus motif VTVLP is the key minimal dimerization motif. The VTVLP motif is highly conserved and likely to be the physiologically relevant interface for all other members of the SLC4 family...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28929319/a-practical-approach-to-hypertension-management-in-diabetes
#3
REVIEW
Altamash Shaikh
Hypertension is one of the most important comorbidities of diabetes, contributing significantly to death and disability and leads to macrovascular and microvascular complications. When assessing the medical priorities for patients with diabetes, treating hypertension should be a primary consideration. Practical approaches to hypertension in diabetes, including individualized targets are discussed, as per stage and complication of diabetes, according to current studies and guidelines. Angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARBs) are the most effective drugs for treating hypertension in diabetes, in the absence of contraindications...
September 19, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28928461/time-dependent-effects-of-ipragliflozin-on-behaviour-and-energy-homeostasis-in-normal-and-type-2-diabetic-rats-continuous-glucose-telemetry-analysis
#4
Hiroyuki Iuchi, Masaya Sakamoto, Daisuke Matsutani, Hirofumi Suzuki, Yosuke Kayama, Norihiko Takeda, Susumu Minamisawa, Kazunori Utsunomiya
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs that promote urinary glucose excretion. Conversely, they cause behavioural changes, such as hyperphagia, that result in a positive energy balance. The relationship between energy homeostasis and SGLT2 inhibitors-induced behavioural changes remains unclear. Here we show that ipragliflozin, a SGLT2 inhibitor, time-dependently affects behaviour and enhances energy expenditure in normal and type 2 diabetic Goto-Kakizaki (GK) rats, using continuous glucose telemetry...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928093/effect-of-sodium-glucose-cotransporter-2-sglt2-inhibition-on-weight-loss-is-partly-mediated-by-liver-brain-adipose-neurocircuitry
#5
Yoshikazu Sawada, Yoshihiko Izumida, Yoshinori Takeuchi, Yuichi Aita, Nobuhiro Wada, EnXu Li, Yuki Murayama, Xiaoying Piao, Akito Shikama, Yukari Masuda, Makiko Nishi-Tatsumi, Midori Kubota, Motohiro Sekiya, Takashi Matsuzaka, Yoshimi Nakagawa, Yoko Sugano, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Hiroaki Suzuki, Hiroaki Yagyu, Yasushi Kawakami, Takashi Kadowaki, Hitoshi Shimano, Naoya Yahagi
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have both anti-diabetic and anti-obesity effects. However, the precise mechanism of the anti-obesity effect remains unclear. We previously demonstrated that the glycogen depletion signal triggers lipolysis in adipose tissue via liver-brain-adipose neurocircuitry. In this study, therefore, we investigated whether the anti-obesity mechanism of SGLT2 inhibitor is mediated by this mechanism. Diet-induced obese mice were subjected to hepatic vagotomy (HVx) or sham operation and loaded with high fat diet containing 0...
September 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28926495/bolstering-your-armamentarium-with-sglt2-inhibitors
#6
Lucia M Novak, Davida F Kruger
Sodium-glucose cotransporter-2 inhibitors have a unique mechanism of action in the kidneys that causes glucosuria, which lowers plasma glucose. They are also associated with reduced body weight and BP, and a low incidence of hypoglycemia. This article reviews the pharmacologic profiles and clinical implications of canagliflozin, dapagliflozin, and empagliflozin.
October 18, 2017: Nurse Practitioner
https://www.readbyqxmd.com/read/28924123/the-improvement-of-the-hepatic-histological-findings-in-a-patient-with-non-alcoholic-steatohepatitis-with-type-2-diabetes-after-the-administration-of-the-sodium-glucose-cotransporter-2-inhibitor-ipragliflozin
#7
Akihiko Takeda, Aya Irahara, Atsuko Nakano, Emi Takata, Yuko Koketsu, Kunie Kimata, Eri Senda, Hajime Yamada, Kazuhito Ichikawa, Takahiro Fujimori, Yoshio Sumida
The patient was a 67-year-old woman with type 2 diabetes and non-alcoholic steatohepatitis (NASH). The administration of the sodium-glucose cotransporter 2 (SGLT2) inhibitor, ipragliflozin improved her liver dysfunction clinically and histologically. The serum alanine aminotransferase (ALT) and ferritin levels decreased to normal limits after treatment for four months. Type IV collagen and hyaluronic acid, both of which were serum fibrotic markers, decreased after treatment. Ultrasonography and computed tomography showed a decrease in the fat deposits in her liver...
September 15, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28923771/differential-expression-of-putative-sodium-dependent-cation-chloride-cotransporters-in-aedes-aegypti
#8
Peter M Piermarini, Daniel C Akuma, John C Crow, Taylor L Jamil, Willa G Kerkhoff, Kenyatta C M F Viel, Christopher M Gillen
The yellow fever mosquito, Aedes aegypti, has three genes that code for proteins with sequence similarity to vertebrate Na(+)-K(+)-Cl(-) cotransporters (NKCCs) of the solute-linked carrier 12 superfamily of cation-chloride cotransporters (CCCs). We hypothesized that these mosquito NKCC orthologues have diverged to perform distinct roles in salt secretion and absorption. In phylogenetic analyses, one protein (aeNKCC1) groups with a Drosophila melanogaster NKCC that mediates salt secretion whereas two others (aeCCC2 and aeCCC3) group with a Drosophila transporter that is not functionally characterized...
September 18, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28919061/efficacy-and-safety-of-dapagliflozin-in-patients-with-inadequately-controlled-type-1-diabetes-depict-1-24-week-results-from-a-multicentre-double-blind-phase-3-randomised-controlled-trial
#9
Paresh Dandona, Chantal Mathieu, Moshe Phillip, Lars Hansen, Steven C Griffen, Diethelm Tschöpe, Fredrik Thorén, John Xu, Anna Maria Langkilde
BACKGROUND: Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor approved for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of dapagliflozin as an add-on to adjustable insulin in patients with inadequately controlled type 1 diabetes. METHODS: DEPICT-1 was a double-blind, randomised, parallel-controlled, three-arm, phase 3, multicentre study done at 143 sites in 17 countries. Eligible patients were aged 18-75 years and had inadequately controlled type 1 diabetes (HbA1c between ≥7·7% and ≤11·0% [≥61·0 mmol/mol and ≤97·0 mmol/mol]) and had been prescribed insulin for at least 12 months before enrolment...
September 13, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28915572/down-regulation-of-ntcp-expression-by-cyclin-d1-in-hepatitis-b-virus-related-hepatocellular-carcinoma-has-clinical-significance
#10
Jingting Kang, Jie Wang, Jin Cheng, Zhiliang Cao, Ran Chen, Huiyu Li, Shuang Liu, Xiangmei Chen, Jianhua Sui, Fengmin Lu
The sodium-dependent taurocholate cotransporter polypeptide (NTCP) has been identified as a liver specific functional receptor for the hepatitis B virus (HBV). Previous studies indicated that the expression of NTCP may be associated with the proliferation status of hepatocytes. However, the involvement of NTCP in hepatocellular carcinoma (HCC) cells proliferation remains unclear. In this study, we confirmed that NTCP was down-regulated in HCC tumor tissues compared with that in the adjacent non-tumor tissues (P < 0...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912902/effects-of-dapagliflozin-on-body-composition-and-liver-tests-in-patients-with-nonalcoholic-steatohepatitis-associated-with-type-2-diabetes-mellitus-a-prospective-open-label-uncontrolled-study
#11
Hiroshi Tobita, Shuichi Sato, Tatsuya Miyake, Shunji Ishihara, Yoshikazu Kinoshita
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an active form of nonalcoholic fatty liver disease. Risk factors for NASH include type 2 diabetes mellitus (T2DM) and obesity. Sodium-glucose cotransporter 2 (SGLT2) inhibitors used to treat T2DM prevent glucose reabsorption in the kidney and increase glucose urinary excretion. Dapagliflozin is a potent, selective SGLT2 inhibitor that reduces hyperglycemia in patients with T2DM and has been demonstrated to reduce some complications associated with NASH in rodent models...
2017: Current Therapeutic Research, Clinical and Experimental
https://www.readbyqxmd.com/read/28904232/effects-of-high-versus-moderate-intensity-training-on-neuroplasticity-and-functional-recovery-after-focal-ischemia
#12
Caroline Pin-Barre, Annabelle Constans, Jeanick Brisswalter, Christophe Pellegrino, Jérôme Laurin
BACKGROUND AND PURPOSE: This study was designed to compare the effects of high-intensity interval training (HIT) and moderate-intensity aerobic training (MOD) on functional recovery and cerebral plasticity during the first 2 weeks after cerebral ischemia. METHODS: Rats were randomized as follows: control (n=15), SHAM (n=9), middle cerebral artery occlusion (n=13), middle cerebral artery occlusion at day 1 (n=7), MOD (n=13), and HIT (n=13). Incremental tests were performed at day 1 (D1) and 14 (D14) to identify the running speed associated with the lactate threshold (SLT) and the maximal speed (Smax)...
September 13, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28904068/empagliflozin-and-clinical-outcomes-in-patients-with-type-2-diabetes-established-cardiovascular-disease-and-chronic-kidney-disease
#13
Christoph Wanner, John M Lachin, Silvio E Inzucchi, David Fitchett, Michaela Mattheus, Jyothis T George, Hans-Juergen Woerle, Uli C Broedl, Maximilian von Eynatten, Bernard Zinman
Background -Empagliflozin, a sodium glucose cotransporter 2 inhibitor, reduced cardiovascular morbidity and mortality in patients with type 2 diabetes and established cardiovascular disease in the EMPA-REG OUTCOME(®) trial. Urinary glucose excretion with empagliflozin decreases with declining renal function, resulting in less potency for glucose lowering in patients with kidney disease. We investigated the effects of empagliflozin on clinical outcomes in patients with type 2 diabetes, established cardiovascular disease and chronic kidney disease...
September 13, 2017: Circulation
https://www.readbyqxmd.com/read/28900540/treatment-of-diabetic-mice-with-the-sglt2-inhibitor-ta-1887-antagonizes-diabetic-cachexia-and-decreases-mortality
#14
Taichi Sugizaki, Shunshun Zhu, Ge Guo, Akiko Matsumoto, Jiabin Zhao, Motoyoshi Endo, Haruki Horiguchi, Jun Morinaga, Zhe Tian, Tsuyoshi Kadomatsu, Keishi Miyata, Hiroshi Itoh, Yuichi Oike
A favorable effect of an inhibitor of the sodium-glucose cotransporter 2 (SGLT2i) on mortality of diabetic patients was recently reported, although mechanisms underlying that effect remained unclear. Here, we examine SGLT2i effects on survival of diabetic mice and assess factors underlying these outcomes. To examine SGLT2i treatment effects in a model of severe diabetes, we fed genetically diabetic db/db mice a high-fat diet and then assessed outcomes including diabetic complications between SGLT2i TA-1887-treated and control mice...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28899222/effects-of-sotagliflozin-added-to-insulin-in-patients-with-type-1-diabetes
#15
Satish K Garg, Robert R Henry, Phillip Banks, John B Buse, Melanie J Davies, Gregory R Fulcher, Paolo Pozzilli, Diane Gesty-Palmer, Pablo Lapuerta, Rafael Simó, Thomas Danne, Darren K McGuire, Jake A Kushner, Anne Peters, Paul Strumph
Background In most patients with type 1 diabetes, adequate glycemic control is not achieved with insulin therapy alone. We evaluated the safety and efficacy of sotagliflozin, an oral inhibitor of sodium-glucose cotransporters 1 and 2, in combination with insulin treatment in patients with type 1 diabetes. Methods In this phase 3, double-blind trial, which was conducted at 133 centers worldwide, we randomly assigned 1402 patients with type 1 diabetes who were receiving treatment with any insulin therapy (pump or injections) to receive sotagliflozin (400 mg per day) or placebo for 24 weeks...
September 13, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28891142/network-meta-analysis-of-lorcaserin-and-oral-hypoglycaemics-for-patients-with-type-2-diabetes-mellitus-and-obesity
#16
L M Neff, M S Broder, D Beenhouwer, E Chang, E Papoyan, Z W Wang
In addition to weight loss, randomized controlled trials have shown improvement in glycaemic control in patients taking lorcaserin. The aim of this study aim was to compare adding lorcaserin or other glucose lowering medications to metformin on weight and glycaemic control. A systematic review and network meta-analysis of randomized controlled trials were conducted. Included studies (published 1990-2014) were of lorcaserin or glucose lowering medications in type 2 diabetic patients compared to placebo or different active treatments...
September 10, 2017: Clinical Obesity
https://www.readbyqxmd.com/read/28891024/resveratrol-supplementation-improves-lipid-and-glucose-metabolism-in-high-fat-diet-fed-blunt-snout-bream
#17
Dingdong Zhang, Yanan Yan, Hongyan Tian, Guangzhen Jiang, Xiangfei Li, Wenbin Liu
Here, we aimed to investigate whether resveratrol (RSV) can ameliorate high-fat diet (HFD)-induced metabolic disorder in fish. Blunt snout bream (Megalobrama amblycephala) with average weight 27.99 ± 0.56 g were fed a normal fat diet (NFD, 5% fat, w/w), a HFD (11% fat), or a HFD supplemented with 0.04, 0.36, or 1.08% RSV for 10 weeks. As expected, fish fed a HFD developed hepatic steatosis, as shown by elevated hepatic and plasma triglycerides, raised whole body fat, intraperitoneal fat ratio and hepatosomatic index, and increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST)...
September 10, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28884600/dapagliflozin-saxagliptin-fixed-dose-tablets-a-new-sodium-glucose-cotransporter-2-and-dipeptidyl-peptidase-4-combination-for-the-treatment-of-type-2-diabetes
#18
Valerie Azzopardi Coppenrath, Tasmina Hydery
OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of the fixed-dose combination (FDC) product, QTERN (dapagliflozin/saxagliptin) tablets. DATA SOURCES: Searches of MEDLINE (1946 to July 1, 2017) were conducted using the keywords QTERN, saxagliptin, and dapagliflozin. Additional data were obtained from the prescribing information, the product dossier, and Clinicaltrials.gov . STUDY SELECTION AND DATA EXTRACTION: All English language articles related to pharmacology, pharmacokinetics, efficacy, or safety of the combination therapy in human subjects were reviewed...
September 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28877076/disruption-of-the-with-no-lysine-kinase-ste20-proline-alanine-rich-kinase-pathway-reduces-the-hypertension-induced-by-angiotensin-ii
#19
Luz G Cervantes-Perez, Maria Castaneda-Bueno, Jose V Jimenez, Norma Vazquez, Lorena Rojas-Vega, Dario R Alessi, Norma A Bobadilla, Gerardo Gamba
OBJECTIVE: The hypertensive effect of angiotensin II (AngII), a peptide hormone, is dependent on its intrarenal actions and the activation of the renal Na-Cl cotransporter (NCC), by AngII requires integrity of the with no lysine kinase/STE20-proline alanine-rich kinase (WNK/SPAK) signaling pathway. Here, we analyzed if the integrity of the WNK/SPAK pathway is required for AngII infusion to induce arterial hypertension. METHODS: We tested the effect of AngII or aldosterone administration on the blood pressure and on pNCC/NCC ratio in SPAK knock-in mice in which the kinase and thus NCC cannot be activated by WNK kinases...
September 14, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28871349/recent-insights-into-pharmacologic-cardiovascular-risk-reduction-in-type-2-diabetes-mellitus
#20
Scott L Purga, Mandeep Sidhu, Michael Farkouh, Joshua Schulman-Marcus
Diabetes mellitus (DM) affects nearly 30 million Americans and carries an increased risk of macrovascular complications of myocardial infarction, stroke, and cardiovascular death. While aggressive cardiovascular risk factor reduction has long been advocated in patients with diabetes, clinical trials have only recently demonstrated that such reductions result in improved outcomes. This review discusses recent evidence for risk reduction strategies and therapies with a focus on the management of glycemia, dyslipidemia, and hypertension...
September 4, 2017: Cardiovascular Drugs and Therapy
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