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Sodium cotransporter

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https://www.readbyqxmd.com/read/29146232/parathyroidectomy-in-patients-with-chronic-kidney-disease-impacts-of-different-techniques-on-the-biochemical-and-clinical-evolution-of-secondary-hyperparathyroidism
#1
Roxana de Fátima Camelo Albuquerque, Cinthia Esbrile Moraes Carbonara, Rita de Cássia T Martin, Luciene Machado Dos Reis, Climério Pereira do Nascimento, Sérgio Samir Arap, Rosa M A Moysés, Vanda Jorgetti, Fábio L M Montenegro, Rodrigo Bueno de Oliveira
BACKGROUND: Parathyroidectomy (PTx) decreases the mortality rate of refractory secondary hyperparathyroidism (rSHP) due to chronic kidney disease. A consensus regarding which techniques of PTx are associated with better outcomes is not available. The aims of this study are to evaluate the clinical and laboratory evolution of 49 hemodialysis patients with rSHP who underwent PTx using different techniques. METHODS: Patients underwent subtotal PTx (sub-PTx) or total PTx with autotransplantation (AT) of 45 (PTx-AT45) or 90 parathyroid fragments (PTx-AT90) and were followed for 12 months...
November 13, 2017: Surgery
https://www.readbyqxmd.com/read/29144539/model-based-evaluation-of-proximal-sodium-reabsorption-through-sglt2-in-health-and-diabetes-and-the-effect-of-inhibition-with-canagliflozin
#2
Jessica A Brady, K Melissa Hallow
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce glucose levels in diabetes by inhibiting renal glucose reabsorption in the proximal tubule (PT), resulting in urinary glucose excretion. A recent large cardiovascular outcomes trial suggested that the SGLT2i empagliflozin may also decrease risk of renal dysfunction. Because sodium (Na) and glucose reabsorption are coupled through SGLT2, it is hypothesized that the renal benefits may be derived from lowering Na reabsorption in the PT, which would lead to favorable renal hemodynamic changes...
November 16, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29142025/cardioprotection-of-dapagliflozin-and-vildagliptin-in-cardiac-reperfusion-injury-rats
#3
Pongpan Tanajak, Piangkwan Sa-Nguanmoo, Sivaporn Sivasinprasan, Savitree Thummasorn, Natthaphat Siri-Angkul, Siriporn Chattipakorn, Nipon Chattipakorn
Sodium-glucose cotransporter 2 inhibitor (SGLT2-i) effects on cardiac ischemia/reperfusion (I/R) injury are unclear. Unlike SGLT2-i, dipeptidyl peptidase 4 inhibitors (DPP4-i) have shown effective cardioprotection in cardiac I/R injury. We aimed to investigate whether SGLT2-i reduces myocardial dysfunction and myocardial injury to a greater extent than DPP4-i in obese-insulin resistant rats with/without cardiac I/R injury. The high fat (HF) diet induced obese-insulin resistant rats were divided into 4 groups and received the following treatments for 28 days: vehicle (HFV); vildagliptin at a dosage of 3 mg/kg/day (HFVil); dapagliflozin at a dosage of 1 mg/kg/day (HFDa); and combination drugs (HFDaVil)...
November 15, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/29141939/dapagliflozin-in-focal-segmental-glomerulosclerosis-a-combined-human-rodent-pilot-study
#4
Harindra Rajasekeran, Heather N Reich, Michelle A Hladunewich, Daniel Cattran, Julie A Lovshin, Yuliya Lytvyn, Petter Bjornstad, Vesta Lai, Josephine Tse, Leslie Cham, Syamantak Majumder, Bridgit B Bowskill, M Golam Kabir, Suzanne L Advani, Ian W Gibson, Manish M Sood, Andrew Advani, David Z I Cherney
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is an important cause of non-diabetic chronic kidney disease (CKD). Sodium glucose cotransporter-2 inhibition (SGLT2i) therapy attenuates the progression of diabetic nephropathy, but it remains unclear whether SGLT2i provides renoprotection in non-diabetic CKD such as FSGS. OBJECTIVE: The primary aim of this pilot study was to determine the effect of 8 weeks of dapagliflozin on GFR in humans and in experimental FSGS...
November 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29139146/effects-of-the-sodium-glucose-cotransporter-2-sglt2-inhibitor-velagliflozin-a-new-drug-with-therapeutic-potential-to-treat-diabetes-in-cats
#5
M Hoenig, M Clark, D J Schaeffer, D Reiche
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are used in the treatment of human diabetics. They increase glucose excretion and correct hyperglycemia. We examined the investigational SGLT2 inhibitor velagliflozin in two groups of six neutered adult obese cats (equal gender distribution). Placebo (Pl) or drug (D; 1 mg/kg) was administered for 35 days. Routine blood examinations, fructosamine, beta-hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), glucagon, adiponectin, and leptin were measured before and after treatment, also water intake, and urinary electrolytes, glucose, and volume...
November 15, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29133604/canagliflozin-for-primary-and-secondary-prevention-of-cardiovascular-events-results-from-the-canvas-program-canagliflozin-cardiovascular-assessment-study
#6
Kenneth W Mahaffey, Bruce Neal, Vlado Perkovic, Dick de Zeeuw, Greg Fulcher, Ngozi Erondu, Wayne Shaw, Elisa Fabbrini, Tao Sun, Qiang Li, Mehul Desai, David R Matthews
BACKGROUND : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that significantly reduces the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in patients with type 2 diabetes mellitus and elevated cardiovascular risk. The comparative effects among participants with and without a history of cardiovascular disease (secondary versus primary prevention) were prespecified for evaluation. METHODS : The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) randomly assigned 10 142 participants with type 2 diabetes mellitus to canagliflozin or placebo...
November 13, 2017: Circulation
https://www.readbyqxmd.com/read/29133602/cardiovascular-outcomes-and-safety-of-empagliflozin-in-patients-with-type-2-diabetes-mellitus-and-peripheral-artery-disease-a-subanalysis-of-empa-reg-outcome
#7
Subodh Verma, C David Mazer, Mohammed Al-Omran, Silvio E Inzucchi, David Fitchett, Uwe Hehnke, Jyothis T George, Bernard Zinman
Peripheral artery disease (PAD) is one of the most common cardiovascular complications in patients with type 2 diabetes mellitus (T2DM)(1) and is a predictor of cardiovascular death.(2) Interventions that reduce cardiovascular complications in this patient population are urgently required. In the EMPA-REG OUTCOME trial, the sodium glucose cotransporter 2 inhibitor empagliflozin reduced the risk of cardiovascular death by 38% (hazard ratio [HR], 0.62; 95% confidence interval [CI] 0.49-0.77]) and hospitalization for heart failure (HHF) by 35% (HR, 0...
November 13, 2017: Circulation
https://www.readbyqxmd.com/read/29131623/iodide-binding-in-sodium-coupled-cotransporters
#8
Ariela Vergara-Jaque, Peying Fong, Jeffrey Comer
Several apical iodide translocation pathways have been proposed for iodide efflux out of thyroid follicular cells, including a pathway mediated by the sodium-coupled monocarboxylate transporter 1 (SMCT1), which remains controversial. Herein, we evaluate structural and functional similarities between SMCT1 and the well-studied sodium-iodide symporter (NIS) that mediates the first step of iodide entry into the thyroid. Free-energy calculations using a force field with electronic polarizability verify the presence of a conserved iodide-binding pocket between the TM2, TM3, and TM7 segments in hNIS, where iodide is coordinated by Phe67, Gln72, Cys91, and Gln94...
November 13, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29131070/pathophysiology-of-post-transplant-hypertension-in-kidney-transplant-focus-on-calcineurin-inhibitors-induced-oxidative-stress-and-renal-sodium-retention-and-implications-with-rhoa-rho-kinase-pathway
#9
Lorenzo A Calò, Verdiana Ravarotto, Francesca Simioni, Elena Naso, Francesco Marchini, Luciana Bonfante, Lucrezia Furian, Paolo Rigotti
Post-transplant hypertension is a common occurrence during treatment with calcineurin inhibitors (CNIs) in kidney transplant population. The pathogenesis of vasoconstriction induced by CNIs involves vascular tone alterations and kidney sodium transport regulation. Among the factors involved a key role is played by the activation of intrarenal renin-angiotensin system with enhanced release of Angiotensin II (Ang II) and increase of oxidative stress. A common pathway between oxidative stress and hypertension induced by CNIs may be identified in the involvement of the activation of RhoA/Rho kinase pathway, key for the induction of hypertension and cardiovascular-renal remodeling, of the oxidative stress mediated increased nitric oxide (NO) metabolism and increased renal sodium retention via increased activity of thiazide-sensitive sodium chloride cotransporter (NCC) in the distal tubule...
October 16, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29130831/a-predominant-oxidative-renal-metabolite-of-empagliflozin-in-male-mice-is-cytotoxic-in-mouse-renal-tubular-cells-but-not-genotoxic
#10
James D Smith, Zimei Huang, Patricia A Escobar, Pamela Foppiano, Hlaing Maw, William Loging, Hongbin Yu, Jonathan A Phillips, Mitchell Taub, Warren W Ku
In a previously reported CD-1 mouse 2-year carcinogenicity study with the sodium glucose cotransporter-2 inhibitor empagliflozin, an increased incidence of renal tubular adenomas and carcinomas was identified only in the male high-dose group. Follow-up investigative studies have shown that the renal tumors in male high-dose mice were preceded by a number of renal degenerative/regenerative findings. Prior cross-species in vitro metabolism studies using microsomes identified an oxidative metabolite (M466/2) predominantly formed in the male mouse kidney and which spontaneously degrades to a metabolite (M380/1) and reactive 4-OH crotonaldehyde (CTA)...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/29126251/evidence-for-a-role-of-pdz-domain-containing-proteins-to-mediate-hypophosphatemia-in-calcium-stone-formers
#11
Kristin J Bergsland, Fredric L Coe, Joan H Parks, John R Asplin, Elaine M Worcester
Background: Hypophosphatemia (HYP) is common among calcium stone formers (SFs) and in rare cases is associated with mutations in sodium-phosphate cotransporters or in Na+/H+ exchanger regulatory factor 1 (NHERF1), but the majority of cases are unexplained. We hypothesized that reduced sodium-phosphate cotransporter activity mediated via NHERF1 or a similar PDZ domain-containing protein, causes HYP. If so, other transport activities controlled by NHERF1, such as NHE3 and URAT1, might be reduced in HYP...
November 6, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29120956/protein-kinase-c%C3%AE-deletion-causes-hypotension-and-decreased-vascular-contractility
#12
Brandi M Wynne, Cameron G McCarthy, Theodora Szasz, Patrick A Molina, Arlene B Chapman, R Clinton Webb, Janet D Klein, Robert S Hoover
AIM: Protein kinase Cα (PKCα) is a critical regulator of multiple cell signaling pathways including gene transcription, posttranslation modifications and activation/inhibition of many signaling kinases. In regards to the control of blood pressure, PKCα causes increased vascular smooth muscle contractility, while reducing cardiac contractility. In addition, PKCα has been shown to modulate nephron ion transport. However, the role of PKCα in modulating mean arterial pressure (MAP) has not been investigated...
November 8, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/29101501/severe-hypernatraemic-dehydration-and-unconsciousness-in-a-care-dependent-inpatient-treated-with-empagliflozin
#13
Georg Gelbenegger, Nina Buchtele, Christian Schoergenhofer, Martin Roeggla, Michael Schwameis
A 66-year-old Caucasian male became unconscious 2 weeks after initiation of add-on therapy with empagliflozin for poorly controlled type 2 diabetes mellitus. The inpatient had recently suffered focal pontine stroke, rendering him bedridden and requiring increased nursing care, including assistance with drinking. The patient had received empagliflozin 10 mg once daily for glycaemic control. Investigations revealed hypernatraemia (164 mmol/l), a urine glucose level of 3935 mg/dl, and a creatinine level of 2...
November 3, 2017: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/29096595/pleiotropic-actions-of-fgf23
#14
Reinhold G Erben
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone, mainly produced by osteoblasts and osteocytes in response to increased extracellular phosphate and circulating vitamin D hormone. Endocrine FGF23 signaling requires co-expression of the ubiquitously expressed FGF receptor 1 (FGFR1) and the co-receptor α-Klotho (Klotho). In proximal renal tubules, FGF23 suppresses the membrane expression of the sodium-phosphate cotransporters Npt2a and Npt2c which mediate urinary reabsorption of filtered phosphate...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/29094264/treating-disease-mechanisms-in-patients-with-heart-failure-and-diabetes-mellitus
#15
REVIEW
Amanda Trang, David Aguilar
PURPOSE OF REVIEW: Diabetes and heart failure commonly coexist and portend worsened prognosis than either disease alone. We explore mechanisms that may serve as potential treatment targets and review the effects of various contemporary glucose-lowering agents on heart failure outcomes. RECENT FINDINGS: Promising data has emerged on sodium-glucose cotransporter 2 (SLGT2) inhibitors as the first class of agents to improve cardiovascular mortality and heart failure outcomes in diabetic individuals both with and without established heart failure...
December 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/29089529/heparin-at-physiological-concentration-can-enhance-peg-free-in-vitro-infection-with-human-hepatitis-b-virus
#16
Gansukh Choijilsuren, Ren-Shiang Jhou, Shu-Fan Chou, Ching-Jen Chang, Hwai-I Yang, Yang-Yuan Chen, Wan-Long Chuang, Ming-Lung Yu, Chiaho Shih
Hepatitis B virus (HBV) is a blood-borne pathogen responsible for chronic hepatitis, cirrhosis, and liver cancer. The mechanism of HBV entry into hepatocytes remains to be investigated. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was discovered as a major HBV receptor based on an in vitro infection system using NTCP-reconstituted HepG2 cells. However, this infection system relies on the compound polyethylene glycol (4% PEG), which is not physiologically relevant to human infection. High concentration of heparin has been commonly used as an inhibitor control for in vitro infection in the field...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29084249/the-effect-of-sodium-glucose-cotransporter-2-sglt2-inhibition-on-the-urinary-proteome
#17
David Cherney, Bruce A Perkins, Yuliya Lytvyn, Hiddo Heerspink, María E Rodríguez-Ortiz, Harald Mischak
Treatment with empagliflozin, an inhibitor of the sodium/glucose cotransporter 2 (SGLT2), is associated with slower progression of diabetic kidney disease. In this analysis, we explored the hypothesis that empagliflozin may have an impact on urinary peptides associated with chronic kidney disease (CKD). In this post-hoc, exploratory analysis, we investigated urine samples obtained from 40 patients with uncomplicated type 1 diabetes (T1D) before and after treatment with empagliflozin for 8 weeks to for significant post-therapy changes in urinary peptides...
2017: PloS One
https://www.readbyqxmd.com/read/29083247/tight-coupling-of-astrocyte-energy-metabolism-to-synaptic-activity-revealed-by-genetically-encoded-fret-nanosensors-in-hippocampal-tissue
#18
Iván Ruminot, Jana Schmälzle, Belén Leyton, L Felipe Barros, Joachim W Deitmer
The potassium ion, K(+), a neuronal signal that is released during excitatory synaptic activity, produces acute activation of glucose consumption in cultured astrocytes, a phenomenon mediated by the sodium bicarbonate cotransporter NBCe1 ( SLC4A4). We have explored here the relevance of this mechanism in brain tissue by imaging the effect of neuronal activity on pH, glucose, pyruvate and lactate dynamics in hippocampal astrocytes using BCECF and FRET nanosensors. Electrical stimulation of Schaffer collaterals produced fast activation of glucose consumption in astrocytes with a parallel increase in intracellular pyruvate and biphasic changes in lactate ...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29080075/current-therapies-that-modify-glucagon-secretion-what-is-the-therapeutic-effect-of-such-modifications
#19
REVIEW
Magnus F Grøndahl, Damien J Keating, Tina Vilsbøll, Filip K Knop
PURPOSE OF REVIEW: Hyperglucagonemia contributes significantly to hyperglycemia in type 2 diabetes and suppressed glucagon levels may increase the risk of hypoglycemia. Here, we give a brief overview of glucagon physiology and the role of glucagon in the pathophysiology of type 2 diabetes and provide insights into how antidiabetic drugs influence glucagon secretion as well as a perspective on the future of glucagon-targeting drugs. RECENT FINDINGS: Several older as well as recent investigations have evaluated the effect of antidiabetic agents on glucagon secretion to understand how glucagon may be involved in the drugs' efficacy and safety profiles...
October 28, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/29076040/sglt2-inhibitors-through-the-windows-of-empa-reg-and-canvas-trials-a-review
#20
REVIEW
Ashu Rastogi, Anil Bhansali
EMPA-REG OUTCOME and CANVAS trials were designed to study the cardiovascular safety of empagliflozin and canagliflozin, respectively. Both studies were sufficiently powered to study the non-inferiority for cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (DM) and showed superiority for major adverse cardiovascular events and composite renal outcomes independent of glycemic control. Further, all patients in EMPA-REG had prior CV events (secondary prevention), compared to CANVAS that also included subjects with no prior CV events, indicating the beneficial effects of canagliflozin in primary prevention of CV events as well...
December 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
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