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Sodium cotransporter

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https://www.readbyqxmd.com/read/28102030/impact-of-sodium-glucose-cotransporter-2-inhibitors-on-nonglycemic-outcomes-in-patients-with-type-2-diabetes
#1
Jennifer M Trujillo, Wesley A Nuffer
The efficacy of the sodium-glucose cotransporter 2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin in reducing hyperglycemia in patients with type 2 diabetes is well documented. In addition, positive effects have been observed with these agents on nonglycemic variables, such as reductions in body weight and blood pressure, which may confer additional health benefits. SGLT2 inhibitors are also associated with evidence of renal-protecting benefits. Furthermore, during the landmark Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) trial, a substantial reduction in major adverse cardiovascular outcomes was demonstrated with empagliflozin therapy...
January 19, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28101242/screening-and-analysis-of-breast-cancer-genes-regulated-by-the-human-mammary-microenvironment-in-a-humanized-mouse-model
#2
Mingjie Zheng, Jue Wang, Lijun Ling, Dandan Xue, Shui Wang, Yi Zhao
Tumor microenvironments play critical regulatory roles in tumor growth. Although mouse cancer models have contributed to the understanding of human tumor biology, the effectiveness of mouse cancer models is limited by the inability of the models to accurately present humanized tumor microenvironments. Previously, a humanized breast cancer model in severe combined immunodeficiency mice was established, in which human breast cancer tissue was implanted subcutaneously, followed by injection of human breast cancer cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100918/cardioprotective-effects-of-sglt2-inhibitors-are-possibly-associated-with-normalization-of-the-circadian-rhythm-of-blood-pressure
#3
REVIEW
Asadur Rahman, Hirofumi Hitomi, Akira Nishiyama
Improvement in cardiovascular (CV) morbidity and mortality in the EMPA-REG OUTCOME study provides new insight into the therapeutic use of sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes. Although SGLT2 inhibitors have several pleiotropic effects, the underlying mechanism responsible for their cardioprotective effects remains undetermined. In this regard, the absence of a nocturnal fall in blood pressure (BP), that is, non-dipping BP, is a common phenomenon in type 2 diabetes and has a crucial role in the pathogenesis of CV morbidity and mortality...
January 19, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28099783/ketosis-and-diabetic-ketoacidosis-in-response-to-sglt2-inhibitors-basic-mechanisms-and-therapeutic-perspectives
#4
REVIEW
Hongyu Qiu, Aleksandra Novikov, Volker Vallon
Inhibitors of the sodium-glucose cotransporter SGLT2 are a new class of anti-hyperglycemic drugs that have been approved for the treatment of type 2 diabetes mellitus (T2DM). These drugs inhibit glucose reabsorption in the proximal tubules of the kidney thereby enhancing glucosuria and lowering blood glucose levels. Additional consequences and benefits include a reduction in body weight, uric acid levels, and blood pressure. Moreover, SGLT2 inhibition can have protective effects on the kidney and cardiovascular system in patients with T2DM and high cardiovascular risk...
January 18, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28094030/glucocorticoid-induced-leucine-zipper-protein-regulates-sodium-and-potassium-balance-in-the-distal-nephron
#5
Priyanka Rashmi, GianLuca Colussi, Michael Ng, Xinhao Wu, Atif Kidwai, David Pearce
Glucocorticoid induced leucine zipper protein (GILZ) is an aldosterone-regulated protein that controls sodium transport in cultured kidney epithelial cells. Mice lacking GILZ have been reported previously to have electrolyte abnormalities. However, the mechanistic basis has not been explored. Here we provide evidence supporting a role for GILZ in modulating the balance of renal sodium and potassium excretion by regulating the sodium-chloride cotransporter (NCC) activity in the distal nephron. Gilz(-/-) mice have a higher plasma potassium concentration and lower fractional excretion of potassium than wild type mice...
January 13, 2017: Kidney International
https://www.readbyqxmd.com/read/28092375/postprandial-macrophage-derived-il-1%C3%AE-stimulates-insulin-and-both-synergistically-promote-glucose-disposal-and-inflammation
#6
Erez Dror, Elise Dalmas, Daniel T Meier, Stephan Wueest, Julien Thévenet, Constanze Thienel, Katharina Timper, Thierry M Nordmann, Shuyang Traub, Friederike Schulze, Flurin Item, David Vallois, Francois Pattou, Julie Kerr-Conte, Vanessa Lavallard, Thierry Berney, Bernard Thorens, Daniel Konrad, Marianne Böni-Schnetzler, Marc Y Donath
The deleterious effect of chronic activation of the IL-1β system on type 2 diabetes and other metabolic diseases is well documented. However, a possible physiological role for IL-1β in glucose metabolism has remained unexplored. Here we found that feeding induced a physiological increase in the number of peritoneal macrophages that secreted IL-1β, in a glucose-dependent manner. Subsequently, IL-1β contributed to the postprandial stimulation of insulin secretion. Accordingly, lack of endogenous IL-1β signaling in mice during refeeding and obesity diminished the concentration of insulin in plasma...
January 16, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28090235/a-possible-mechanism-for-renoprotective-effect-of-sodium-glucose-cotransporter-2-inhibitor-elevation-of-erythropoietin-production
#7
Hidekatsu Yanai, Hisayuki Katsuyayama
No abstract text is available yet for this article.
February 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28090234/increased-hematocrit-during-sodium-glucose-cotransporter-2-inhibitor-therapy
#8
Samuel N Heyman, Mogher Khamaisi, Christian Rosenberger, Auryan Szalat, Zaid Abassi
No abstract text is available yet for this article.
February 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28090231/effects-of-ipragliflozin-on-diabetic-nephropathy-and-blood-pressure-in-patients-with-type-2-diabetes-an-open-label-study
#9
Daisuke Ito, Emi Ikuma-Suwa, Kazuyuki Inoue, Kimie Kaneko, Morifumi Yanagisawa, Kouichi Inukai, Mitsuhiko Noda, Akira Shimada
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are novel agents used to treat type 2 diabetic patients. We investigated the efficacy of the SGLT2 inhibitor ipragliflozin on diabetic nephropathy in Japanese patients with type 2 diabetes. METHODS: A 50 mg dose of ipragliflozin was administered for 24 weeks to 50 patients with type 2 diabetes who were concomitantly managed with diet and exercise therapy alone or antidiabetic medications other than SGLT2 inhibitors...
February 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28090050/euglycemic-diabetic-ketoacidosis-with-persistent-diuresis-treated-with-canagliflozin
#10
Junichiro Adachi, Yuusuke Inaba, Chisato Maki
Diabetic ketoacidosis is characterized by hyperglycemia, anion-gap acidosis, and increased plasma ketones. After the resolution of hyperglycemia, persistent diuresis is rare. We herein report the case of a 27-year-old Asian woman with type 2 diabetes who was treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin) who developed euglycemic diabetic ketoacidosis and persistent diuresis in the absence of hyperglycemia. Physicians should consider euglycemic diabetic ketoacidosis in the differential diagnosis of patients treated with SGLT2 inhibitors...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28088910/sodium-glucose-cotransporter-2-inhibitors-sglt2i-their-role-in-cardiometabolic-risk-management
#11
Niki Katsiki, Dimitri P Mikhailidis, Michael J Theodorakis
BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel category of oral antidiabetic drugs that inhibit renal glucose reabsorption and increase renal glucose excretion, thus lowering plasma glucose levels. This unique mechanism of SGLT2i action is insulin independent, thus improving glycemic control without promoting hypoglycemia in the absence of exogenously administered insulin. METHODS: The present narrative review addresses the putative associations between SGLT2i and several cardiovascular (CV) and microvascular risk factors, as well as their effects on cardiac and renal function...
January 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28081591/new-perspectives-of-biomarkers-for-the-management-of-chronic-hepatitis-b
#12
REVIEW
Chih-Lin Lin, Jia-Horng Kao
With recent advances in molecular and genomic investigations, the impact of hepatitis B viral and host factors on the progression of chronic HBV infection has been explored. For viral factors, hepatitis B viral load is a strong predictor for liver disease progression. Hepatitis B viral kinetics appear to be important for successful anti-viral therapy. Serum HBsAg level serves as a complementary marker to viral load for the prediction of HBV-related adverse outcomes in patients with low viral load. In those with low viral load, high serum HBsAg level is associated with higher risks of cirrhosis and HCC...
December 2016: Clinical and Molecular Hepatology
https://www.readbyqxmd.com/read/28077257/real-world-effectiveness-and-safety-of-dapagliflozin-therapy-added-to-a-glp1-receptor-agonist-in-patients-with-type-2-diabetes
#13
J J Gorgojo-Martínez, C Serrano-Moreno, A Sanz-Velasco, G Feo-Ortega, F Almodóvar-Ruiz
BACKGROUND AND AIM: To evaluate the effectiveness and safety of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, dapagliflozin, in patients with type 2 diabetes mellitus (T2DM) and background glucagon-like peptide-1 receptor agonist (GLP1-RA) therapy. METHODS AND RESULTS: This is a 12-month, real-world observational study, which assessed the effectiveness and safety of dapagliflozin in patients with T2DM and background GLP1-RA therapy. The main outcome measures were changes in A1C and weight at 6 and 12 months from baseline...
November 23, 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28076808/spatiotemporal-modeling-of-triggering-and-amplifying-pathways-in-glp-1-secreting-intestinal-l-cells
#14
Alessia Tagliavini, Morten Gram Pedersen
Glucagon-like peptide 1 (GLP-1) is secreted by intestinal L-cells, and augments glucose-induced insulin secretion, thus playing an important role in glucose control. The stimulus-secretion pathway in L-cells is still incompletely understood and a topic of debate. It is known that GLP-1 secreting cells can sense glucose to promote electrical activity either by the electrogenic sodium-glucose cotransporter SGLT1, or by closure of ATP-sensitive potassium channels after glucose metabolism. Glucose also has an effect on GLP-1 secretion downstream of electrical activity...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28065547/comparison-of-the-diabetes-guidelines-from-the-ada-easd-and-the-aace-ace
#15
Susan Cornell
OBJECTIVE: To compare recent diabetes guideline updates from the American Diabetes Association-European Association for the Study of Diabetes (ADA/EASD) and the American Association of Clinical Endocrinologists-American College of Endocrinology (AACE/ACE). SUMMARY: The ADA/EASD guideline continues to advocate a stepwise approach to glycemic control that initiates with metformin and intensifies treatment incrementally to dual and triple therapy at 3-month intervals until the patient is at their individualized goal...
January 5, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28063802/resolving-the-kga1c-paradox-in-the-management-of-type-2-diabetes-mellitus
#16
REVIEW
Jaime Davidson, Sanjay Kalra, Vikram Singh, Mayuresh Fegade, Gursimran Singh, Amey Mane
Excess body weight is a leading cause of metabolic complications such as hypertension and dyslipidemia in T2DM patients. Available antihyperglycemic agents have minimal or no impact on these complications and a majority are known to trigger weight gain, thereby exerting a paradoxical effect on overall metabolic status. This review introduces the concept of 'KgA1c paradox' and underscores the significance of resolving this paradox for comprehensive T2DM management. It provides a therapeutic rationale for inclusion of sodium glucose cotransporter 2 inhibitors in the T2DM treatment algorithm as these agents have demonstrated favorable glycemic effects along with reduction in body weight...
December 13, 2016: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28055075/oral-pharmacologic-treatment-of-type-2-diabetes-mellitus-a-clinical-practice-guideline-update-from-the-american-college-of-physicians
#17
Amir Qaseem, Michael J Barry, Linda L Humphrey, Mary Ann Forciea
Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on oral pharmacologic treatment of type 2 diabetes in adults. This guideline serves as an update to the 2012 ACP guideline on the same topic. This guideline is endorsed by the American Academy of Family Physicians. Methods: This guideline is based on a systematic review of randomized, controlled trials and observational studies published through December 2015 on the comparative effectiveness of oral medications for type 2 diabetes...
January 3, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28045524/discovery-of-lx2761-a-sodium-dependent-glucose-cotransporter-1-sglt1-inhibitor-restricted-to-the-intestinal-lumen-for-the-treatment-of-diabetes
#18
Nicole C Goodwin, Zhi-Ming Ding, Bryce A Harrison, Eric D Strobel, Angela L Harris, Melinda Smith, Andrea Y Thompson, Wendy Xiong, Faika Mseeh, Debra J Bruce, Damaris Diaz, Suma Gopinathan, Ling Li, Emily O'Neill, Mary Thiel, Alan G E Wilson, Kenneth G Carson, David R Powell, David B Rawlins
The increasing number of people afflicted with diabetes throughout the world is a major health issue. Inhibitors of the sodium-dependent glucose cotransporters (SGLT) have appeared as viable therapeutics to control blood glucose levels in diabetic patients. Herein we report the discovery of LX2761, a locally-acting SGLT1 inhibitor that is highly potent in vitro and delays intestinal glucose absorption in vivo to improve glycemic control.
January 3, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28043731/acetazolamide-and-hydrochlorothiazide-followed-by-furosemide-versus-furosemide-and-hydrochlorothiazide-followed-by-furosemide-for-the-treatment-of-adults-with-nephrotic-edema-a-randomized-trial
#19
Mohammad Amin Fallahzadeh, Banafshe Dormanesh, Mohammad Kazem Fallahzadeh, Jamshid Roozbeh, Mohammad Hossein Fallahzadeh, Mohammad Mahdi Sagheb
BACKGROUND: Nephrotic edema is considered refractory if it does not respond to maximum or near-maximum doses of loop diuretics. This condition can be treated with loop diuretics and thiazides. However, animal studies show that the simultaneous downregulation of pendrin with acetazolamide and inhibition of the sodium-chloride cotransporter with hydrochlorothiazide generates significant diuresis, and furosemide administration following a pendrin inhibitor potentiates furosemide's diuretic effect...
December 30, 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28043708/emerging-roles-of-sodium-glucose-cotransporter-2-inhibitors-in-cardiology
#20
REVIEW
Atsushi Tanaka, Koichi Node
The ultimate goal of treatment in people with diabetes mellitus is to prevent development of cardiovascular (CV) disease, resulting in prolongation of healthy life expectancy. Although impaired glycemic metabolism has a central role in its pathology, a number of studies have demonstrated that remedy for its imbalance cannot necessarily be accomplished as a therapeutic goal. A comprehensive medical approach against multi-factorial pathologies in diabetes, such as insulin resistance, obesity, hypertension, and dyslipidemia, in addition to diet and exercise therapy should be rather performed in the routine clinical setting...
December 30, 2016: Journal of Cardiology
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