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Sodium cotransporter

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https://www.readbyqxmd.com/read/28731330/mapping-functionally-important-residues-in-the-na-dicarboxylate-cotransporter-nadc1
#1
Claire Colas, Avner Schlessinger, Ana M Pajor
Transporters from the SLC13 family couple the transport of 2-4 Na+ ions with a di- or tricarboxylate, such as succinate or citrate. We have previously modeled mammalian SLC13 members including the Na+/dicarboxylate cotransporter NaDC1 (SLC13A2), based on a structure of the bacterial homolog VcINDY in an inward-facing conformation with one sodium ion bound at the Na1 site. In the present study, we modeled the outward-facing conformation of the rabbit and human NaDC1 (rbNaDC1 and hNaDC1) using an outward-facing model of VcINDY as a template, and identified residues in or near the putative Na2 and Na3 cation binding sites...
July 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28730878/investigational-drugs-in-development-for-hepatitis-d
#2
Mario Rizzetto
Treatment of chronic hepatitis D still relies on Interferon. To improve efficacy, new therapeutic strategies are in development which aim to deprive the Hepatitis D Virus (HDV) of functions of the Hepatitis B Virus and of the host required for its life-cycle. Areas covered: The therapeutic options are; 1) The inhibition of the farnesylation of the large HD-protein permissive of virion assembly with Lonafarnib, 2) The blocking of HBsAg entry into cells with Myrcludex B via the inhibition of the Sodium Taurocholate Cotransporting Receptor, to prevent the spreading of HDV to uninfected hepatocytes, 3) The reduction of subviral HBsAg particles by REP 2139, leading to diminished virion morphogenesis ...
July 21, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28726152/cardiovascular-outcome-trial-update-in-diabetes-new-evidence-remaining-questions
#3
REVIEW
Rebecca Herbst, Wilburn Bolton, Afreen Shariff, Jennifer B Green
PURPOSE OF REVIEW: Seven trials of new agents to treat type 2 diabetes (T2DM) have been performed to assess cardiovascular (CV) safety. A significant amount of information regarding the effects of drugs in three classes is available, with new data from multiple other trials expected shortly. This article provides a summary of recently completed trials. RECENT FINDINGS: The dipeptidyl peptidase-4 inhibitors studied thus far do not alter the risk of major adverse CV events (MACE)...
September 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28725912/sglt2-inhibitors-and-risk-of-cancer-in-type-2-diabetes-a-systematic-review-and-meta-analysis-of-randomised-controlled-trials
#4
REVIEW
Huilin Tang, Qi Dai, Weilong Shi, Suodi Zhai, Yiqing Song, Jiali Han
AIMS/HYPOTHESIS: The association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and the risk of cancer in individuals with type 2 diabetes remains uncertain. This study aimed to evaluate the risk of cancer associated with SGLT2 inhibitor treatment of type 2 diabetes. METHODS: We systematically searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to 15 February 2017 to identify eligible randomised controlled trials (RCTs) that report cancer events in individuals with type 2 diabetes treated with SGLT2 inhibitors for at least 24 weeks...
July 19, 2017: Diabetologia
https://www.readbyqxmd.com/read/28720798/neuroprotective-effect-of-5-aminolevulinic-acid-against-low-inorganic-phosphate-in-neuroblastoma-sh-sy5y-cells
#5
Naoko Takase, Masatoshi Inden, Shin-Ichiro Sekine, Yumi Ishii, Hiroko Yonemitsu, Wakana Iwashita, Hisaka Kurita, Yutaka Taketani, Isao Hozumi
PiT-1 (encoded by SLC20A1) and PiT-2 (encoded by SLC20A2) are type-III sodium-dependent phosphate cotransporters (NaPiTs). Recently, SLC20A2 mutations have been found in patients with idiopathic basal ganglia calcification (IBGC), and were predicted to bring about an inability to transport Pi from the extracellular environment. Here we investigated the effect of low Pi loading on the human neuroblastoma SH-SY5Y and the human glioblastoma A172 cell lines. The results show a different sensitivity to low Pi loading and differential regulation of type-III NaPiTs in these cells...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717146/concise-and-stereodivergent-synthesis-of-carbasugars-reveals-unexpected-structure-activity-relationship-sar-of-sglt2-inhibition
#6
Wai-Lung Ng, Ho-Chuen Li, Kit-Man Lau, Anthony K N Chan, Clara Bik-San Lau, Tony K M Shing
Carbasugar sodium-glucose cotransporter 2 (SGLT2) inhibitors are highly promising drug candidates for the treatment of Type 2 diabetes mellitus (T2DM). However, the clinical usage of carbasugar SGLT2 inhibitors has been underexplored, due to the lengthy synthetic routes and the lack of structure-activity relationship (SAR) studies of these compounds. Herein, we report a concise and stereodivergent synthetic route towards some novel carbasugar SGLT2 inhibitors, featuring an underexploited, regioselective, and stereospecific palladium-catalyzed allyl-aryl coupling reaction...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717041/activation-of-sting-in-hepatocytes-suppresses-the-replication-of-hepatitis-b-virus
#7
Fang Guo, Liudi Tang, Sainan Shu, Mohit Sehgal, Muhammad Sheraz, Bowei Liu, Qiong Zhao, Junjun Cheng, Xuesen Zhao, Tianlun Zhou, Jinhong Chang, Ju-Tao Guo
Induction of interferon and proinflammatory cytokines is a hallmark of the infection of many different viruses. However, hepatitis B virus (HBV) does not elicit a detectable cytokine response in infected hepatocytes. In order to investigate the molecular mechanism underlying the innate immune evasion, a functional cGAS-STING pathway was reconstituted in a human hepatoma cell line supporting tetracycline-inducible HBV replication. It was demonstrated that induction of HBV replication neither activated nor inhibited this cytosolic DNA sensing pathway...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28708480/optimizing-diabetes-treatment-in-the-presence-of-obesity
#8
REVIEW
Mary Angelynne Esquivel, M Cecilia Lansang
Evidence of a neurophysiologic mechanism that involves hormones from adipocytes, pancreatic islet cells, and the gastrointestinal tract implicated in both obesity and diabetes has led to a search for drugs that not only either target obesity and diabetes or reduce hemoglobin A1c, but also have weight loss as a potential side effect. The authors review medications approved for the treatment of type 2 diabetes mellitus (including pramlintide, also approved for type 1 diabetes) that also have weight loss as a side effect...
July 2017: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/28703316/the-effect-of-renal-impairment-on-the-pharmacokinetics-and-pharmacodynamics-of-ertugliflozin-in-subjects-with-type-2-diabetes-mellitus
#9
V Sahasrabudhe, S G Terra, A Hickman, D Saur, H Shi, M O'Gorman, Z Zhou, D L Cutler
Ertugliflozin is a highly selective and potent inhibitor of the sodium-glucose cotransporter 2 in development for the treatment of type 2 diabetes mellitus. The glycemic efficacy of sodium-glucose cotransporter 2 inhibitors such as ertugliflozin depends on glucose filtration through the kidney. This phase 1, open-label study evaluated the effect of renal impairment on the pharmacokinetics, pharmacodynamics, and tolerability of ertugliflozin (15 mg) in type 2 diabetes mellitus and healthy subjects with normal renal function (estimated glomerular filtration rate not normalized for body surface area ≥90 mL/min) and type 2 diabetes mellitus subjects with mild (60-89 mL/min), moderate (30-59 mL/min), or severe (<30 mL/min) renal impairment (n = 36)...
July 13, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28700666/effects-of-kluyveromyces-marxianus-supplementation-on-immune-responses-intestinal-structure-and-microbiota-in-broiler-chickens
#10
Weiwei Wang, Zhui Li, Zengpeng Lv, Beibei Zhang, Hong Lv, Yuming Guo
To investigate the effects of Kluyveromyces marxianus on immune responses, intestinal structure and microbiota in broilers, 840 1-d-old broiler chicks were randomly divided into seven groups (eight replicates) and were fed basal diets without or with 0.25, 0.50, 1.0, 1.5, 2.0, and 2.5 g/kg of K. marxianus (2.0×1010 CFU/g). Serum and intestine samples were collected at 21 d of age. The results showed that increasing K. marxianus addition linearly reduced feed conversion ratio but linearly elevated relative thymus weight, as well as quadratically increased serum lysozyme and IgG levels, with the medium dose (1...
2017: PloS One
https://www.readbyqxmd.com/read/28699798/durability-of-response-to-dapagliflozin-a-review-of-long-term-efficacy-and-safety
#11
Serge Jabbour
BACKGROUND: Due to the chronic nature of type 2 diabetes (T2D), it is essential for an antidiabetic drug to have durable efficacy and a good long-term safety profile. Dapagliflozin is a member of a unique class of antidiabetic drugs that inhibit the sodium-glucose cotransporter 2 (SGLT-2) in the renal tubules and have an insulin-independent mechanism of action. In short-term studies (≤24 weeks), dapagliflozin reduced glycated hemoglobin (A1c), weight, and systolic blood pressure, and had a good safety profile...
July 12, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28683796/effectiveness-of-dapagliflozin-on-vascular-endothelial-function-and-glycemic-control-in-patients-with-early-stage-type-2-diabetes-mellitus-defence-study
#12
Fumika Shigiyama, Naoki Kumashiro, Masahiko Miyagi, Kayoko Ikehara, Eiichiro Kanda, Hiroshi Uchino, Takahisa Hirose
BACKGROUND: Recent studies reported that sodium glucose cotransporter 2 (SGLT2) inhibitors can potentially reduce the risk of cardiovascular mortality in patients with type 2 diabetes mellitus (T2DM). However, there is little or no information on the therapeutic effects of SGLT2 inhibitors on the progression of atherosclerosis. This dapagliflozin effectiveness on vascular endothelial function and glycemic control (DEFENCE) study was designed to determine the effects of dapagliflozin, a SGLT2 inhibitor, on endothelial function in patients with early-stage T2DM...
July 6, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28682870/long-term-efficacy-and-safety-of-sodium-glucose-cotransporter-2-inhibitors-as-add-on-to-metformin-treatment-in-the-management-of-type-2-diabetes-mellitus-a-meta-analysis
#13
Jian Li, Yanping Gong, Chunlin Li, Yanhui Lu, Yu Liu, Yinghong Shao
BACKGROUND: Drug intensification is often required for patients with type 2 diabetes mellitus on stable metformin therapy. Among the potential candidates for a combination therapy, sodium-glucose transporter-2 (SGLT2) inhibitors have shown promising outcomes. This meta-analysis was performed to compare the efficacy and safety of SGLT2 inhibitors with non-SGLT2 combinations as add-on treatment to metformin. METHODS: Literature search was carried out in multiple electronic databases for the acquisition of relevant randomized controlled trials (RCTs) by following a priori eligibility criteria...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28679838/fluorocitrate-mediated-depolarization-of-astrocytes-in-the-retrotrapezoid-nucleus-stimulates-breathing
#14
Cleyton R Sobrinho, Christopher M Gonçalves, Ana C Takakura, Daniel K Mulkey, Thiago S Moreira
Evidence indicates that CO2/H(+)-evoked ATP released from retrotrapezoid nucleus (RTN) astrocytes modulates the activity of CO2-sensitive neurons. RTN astrocytes also sense H+ by inhibition of Kir4.1 channels; however, the relevance of this pH-sensitive current remains unclear since ATP release appears to involve CO2-dependent gating of connexin 26 hemichannels. Considering that depolarization mediated by H(+) inhibition of Kir4.1 channels is expected to increase sodium bicarbonate cotransporter (NBC) conductance and favor Ca(2+) influx via the sodium calcium exchanger (NCX), we hypothesize that depolarization in the presence of CO2 is sufficient to facilitate ATP release and enhance respiratory output...
July 5, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28674356/atypical-ketoacidosis-and-protracted-hyperglycosuria-after-treatment-with-ipragliflozin-an-sglt2-inhibitor
#15
Masaaki Miyauchi, Masao Toyoda, Masafumi Fukagawa
We herein present the case of a 21-year-old diabetic obese woman who developed ketoacidosis following the administration of ipragliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor. At the time of admission, although her serum glucose level was only 175 mg/dL, laboratory tests showed ketoacidosis. Interestingly, hyperglycosuria persisted, even after the discontinuation of ipragliflozin. This is the first report of non-hyperglycemic ketoacidosis that might have been caused by protracted hyperglycosuria after the discontinuation of ipragliflozin...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28671793/-gliptin-gliflozin-combination-for-treating-type-2-diabetes
#16
André J Scheen, Nicolas Paquot
Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycaemia. Combining a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGT2i) appears to be an attractive approach because the two drugs exert different and potentially complementary glucose-lowering effects. Dual therapy (initial combination or stepwise approach) is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin...
August 24, 2016: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28671791/-cardiovascular-protection-of-patients-with-type-2-diabetes-from-empa-reg-outcome-to-leader
#17
André J Scheen, Caroline Wallemacq, Bernard Jandrain, Philippe Ernest
Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, an inhibitor of sodium-glucose type 2 (SGLT2) cotransporters, in EMPA-REG OUTCOME, and liraglutide, an agonist of glucagon-like peptide-1 (GLP-1) receptors, in LEADER, showed a significant reduction in major cardiovascular events (- 14 and - 13 %, respectively), cardiovascular mortality (- 38 and - 22 %, respectively) and all-cause mortality (- 32 and - 15 %, respectively)...
August 24, 2016: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28670136/sodium-glucose-cotransporter-2-inhibition-and-acidosis-in-patients-with-type-2-diabetes-a-review-of-us-fda-data-and-possible-conclusions
#18
John A D'Elia, Alissa R Segal, George P Bayliss, Larry A Weinrauch
OBJECTIVE: To evaluate whether adverse event reports to the US Food and Drug Administration on incidents of ketoacidosis from use of sodium glucose cotransport inhibitors (SGLT2 inhibitors) provide insight into ways this new class of drugs is being prescribed with other antihyperglycemic agents; to examine possible mechanisms to explain ketoacidosis. DESIGN AND METHODS: Reports of adverse events concerned to SGLT2 inhibitors, namely, empagliflozin, dapagliflozin, and canagliflozin were obtained under the Freedom of Information Act for 5 years ending in August 31, 2015...
2017: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/28669625/clinical-risk-factors-predicting-genital-fungal-infections-with-sodium-glucose-cotransporter-2-inhibitor-treatment-the-abcd-nationwide-dapagliflozin-audit
#19
Ken Yan Thong, Mahender Yadagiri, Dennis Joseph Barnes, David Stuart Morris, Tahseen Ahmad Chowdhury, Ling Ling Chuah, Anthony Michael Robinson, Stephen Charles Bain, Karen Ann Adamson, Robert Elford John Ryder
INTRODUCTION: Treatment of type 2 diabetes with sodium-glucose cotransporter 2 (SGLT2) inhibitors may result in genital fungal infections. We investigated possible risk factors for developing such infections among patients treated with the SGLT2 inhibitor dapagliflozin. METHODS: The Association of British Clinical Diabetologists (ABCD) collected data on patients treated with dapagliflozin in routine clinical practice from 59 diabetes centres. We assessed possible associations of patient's age, diabetes duration, body mass index, glycated haemoglobin, renal function, patient sex, ethnicity and prior genital fungal infection, urinary tract infection, urinary incontinence or nocturia, with the occurrence of ≥1 genital fungal infection within 26 weeks of treatment...
June 29, 2017: Primary Care Diabetes
https://www.readbyqxmd.com/read/28662890/diabetic-ketoacidosis-in-patients-under-treatment-with-sodium-glucose-cotransporter-type-2-inhibitors
#20
José Antonio López Medina, Carmen Hernández García, Javier Espíldora Hernández
No abstract text is available yet for this article.
June 26, 2017: Medicina Clínica
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