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Glucose reabsorption

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https://www.readbyqxmd.com/read/28639760/-euglycemic-ketoacidosis-a-complication-of-sglt2-inhibitors
#1
Aki Mizuno, Sanaz Lolachi, Alain Pernet
Sodium-glucose cotransporter 2 (SGLT2) inhibitors constitute a new category of oral antidiabetics recently indicated for the treatment of type 2 diabetes. Their mechanism of action (inhibition of renal reabsorption of glucose) and the fact that they do not induce hypoglycemia (as monotherapy) make their clinical use interesting. Various adverse events have however been reported regarding these drugs with the euglycemic ketoacidosis being the most serious. In this article we aim to review the possible mechanism of this side effect and recommendations for use of SGLT2 inhibitors by means of a case report...
May 31, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28630133/dual-regulation-of-gluconeogenesis-by-insulin-and-glucose-in-the-proximal-tubules-of-the-kidney
#2
Motohiro Sasaki, Takayoshi Sasako, Naoto Kubota, Yoshitaka Sakurai, Iseki Takamoto, Tetsuya Kubota, Reiko Inagi, George Seki, Moritaka Goto, Kohjiro Ueki, Masaomi Nangaku, Takahito Jomori, Takashi Kadowaki
Growing attention has been focused on the roles of the proximal tubules (PTs) of the kidney in glucose metabolism, including the mechanism of regulation of gluconeogenesis. Here, we found that PT-specific IRS1/2 double-knockout mice, established by using the newly generated sodium-glucose cotransporter-2 (SGLT2)-Cre transgenic mice, exhibited impaired insulin signaling and upregulated gluconeogenic gene expression and renal gluconeogenesis, resulting in systemic insulin resistance. On the other hand, in streptozotocin-treated mice, although insulin action was impaired in the PTs, the gluconeogenic gene expression was unexpectedly downregulated in the renal cortex, which was restored by administration of an SGLT1/2 inhibitor...
June 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28611861/effects-of-six-kinds-of-sodium-glucose-cotransporter-2-inhibitors-on-metabolic-parameters-and-summarized-effect-and-its-correlations-with-baseline-data
#3
Hidekatsu Yanai, Mariko Hakoshima, Hiroki Adachi, Akiko Kawaguchi, Yoko Waragai, Tadanao Harigae, Yoshinori Masui, Kouki Kakuta, Hidetaka Hamasaki, Hisayuki Katsuyama, Tomoko Kaga, Akahito Sako
BACKGROUND: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) blocks reabsorption of glucose by inhibiting SGLT2 in kidney, promotes the renal excretion of glucose and improves blood glucose control without requiring insulin secretion. Anti-atherosclerotic effects of SGLT2is have not been fully elucidated until today. METHODS: We retrospectively picked up patients with type 2 diabetes who had been continuously prescribed SGLT2i for 3 months or more between April 2014 and December 2016 by a chart-based analysis, and compared metabolic parameters including coronary risk factors before the SGLT2i treatment with the data at 3 and 6 months after the SGLT2i treatment started...
July 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28598954/role-of-the-sympathetic-nervous-system-in-regulation-of-the-sodium-glucose-cotransporter-2
#4
Vance B Matthews, Rosemary H Elliot, Caroline Rudnicka, Jana Hricova, Lakshini Herat, Markus P Schlaich
BACKGROUND: The sympathetic nervous system (SNS) regulates glucose metabolism in various organs including the kidneys. The sodium glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in renal proximal tubules and its inhibition has been shown to improve glucose control, cardiovascular and renal outcomes. We hypothesized that SNS-induced alterations of glucose metabolism may be mediated via regulation of SGLT2. METHOD: We used human renal proximal tubule cells to investigate the effects of noradrenaline on SGLT2 regulation...
June 8, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28596840/novel-sglt2-inhibitor-first-in-man-studies-of-antisense-compound-is-associated-with-unexpected-renal-effects
#5
Leonie van Meer, Marloes van Dongen, Matthijs Moerland, Marieke de Kam, Adam Cohen, Jacobus Burggraaf
The antisense compound ISIS 388626 selectively inhibits renal glucose reabsorption by inhibiting the sodium-glucose cotransporter-2 (SGLT2) mRNA expression. It is developed as an insulin-independent treatment approach for type 2 diabetes mellitus (T2DM). The safety, tolerability, pharmacokinetics, and pharmacodynamics after subcutaneous administration of the drug were planned to be evaluated in healthy volunteers in a single-ascending-dose study (50-400 mg) and a multiple-ascending-dose study (6 weeks; weekly doses of 50-400 mg with loading dose regimen of three doses during the first week)...
February 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28592437/characterization-of-the-transport-activity-of-sglt2-map17-the-renal-low-affinity-na-glucose-cotransporter
#6
Michael J Coady, Bernadette Wallendorff, Jean-Yves Lapointe
The cotransporter SGLT2 is responsible for 90% of the renal glucose reabsorption and we recently shown that MAP17 appears to work as a required beta subunit. We report in the present paper a detailed functional characterisation of human SGLT2 in co-expression with human MAP17 in Xenopus laevis oocytes. Addition of external glucose generates a large inward current in the presence of Na confirming an electrogenic transport mechanism. At a membrane potential of -50 mV, SGLT2 affinity constants for glucose and Na are 3...
June 7, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28584109/dapagliflozin-suppresses-glucagon-signaling-in-rodent-models-of-diabetes
#7
May-Yun Wang, Xinxin Yu, Young Lee, Sara Kay McCorkle, Shiuhwei Chen, Jianping Li, Zhao V Wang, Jaime A Davidson, Philipp E Scherer, William L Holland, Roger H Unger, Michael G Roth
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of antidiabetic drug used for the treatment of diabetes. These drugs are thought to lower blood glucose by blocking reabsorption of glucose by SGLT2 in the proximal convoluted tubules of the kidney. To investigate the effect of inhibiting SGLT2 on pancreatic hormones, we treated perfused pancreata from rats with chemically induced diabetes with dapagliflozin and measured the response of glucagon secretion by alpha cells in response to elevated glucose...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28577741/-role-of-the-kidneys-in-glucose-homeostasis-implication-of-sodium-glucose-cotransporter-2-sglt2-in-diabetes-mellitus-treatment
#8
Jean Girard
Kidney plays an important role in glucose homeostasis, both in the post-absorptive and postprandial period. Kidney produces glucose by gluconeogenesis in the renal cortex and uses glucose for covering energy needs of the medulla. Kidney participates also to the reabsorption of filtered glucose in order the terminal urine was devoided of glucose, as long as blood glucose did not exceed 180mg/dL. Reabsorption of glucose is mediated by sodium-glucose cotransporters (SGLT1 et SGLT2) expressed in S1 and S3 segments of proximal tubule...
April 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/28536217/caution-advised-with-dapagliflozin-in-the-setting-of-male-urinary-tract-outlet-obstruction
#9
Victoria Hall, Jason Kwong, Douglas Johnson, Elif Ilhan Ekinci
We describe an adverse outcome in a 70-year-old man with type 2 diabetes mellitus treated with sodium-glucose cotransporter type 2 (SGLT2) inhibitor dapagliflozin. SGLT2 inhibitors act in the proximal tubules to prevent glucose reabsorption and induce urinary glucose excretion, they have been associated with increased risk of urinary tract infection (UTI). Our patient presented to hospital with Escherichia coli septicaemia with positive urine and blood cultures on the background of two previous UTIs occurring post commencement of dapagliflozin in the community...
May 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28511711/sglt2-inhibitors-a-novel-choice-for-the-combination-therapy-in-diabetic-kidney-disease
#10
REVIEW
Honghong Zou, Baoqin Zhou, Gaosi Xu
Diabetic kidney disease (DKD) is the most common cause of end stage renal disease. The comprehensive management of DKD depends on combined target-therapies for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral hypoglycemic agents acted on renal proximal tubules, suppress glucose reabsorption and increase urinary glucose excretion. Besides improvements in glycemic control, they presented excellent performances in direct renoprotective effects and the cardiovascular (CV) safety by decreasing albuminuria and the independent CV risk factors such as body weight and blood pressure, etc...
May 16, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28506519/sodium-glucose-co-transporters-and-their-inhibition-clinical-physiology
#11
REVIEW
Ele Ferrannini
Sodium-glucose cotransporter-2 (SGLT2) is selectively expressed in the human kidney, where it executes reabsorption of filtered glucose with a high capacity; it may be overactive in patients with diabetes, especially in the early, hyperfiltering stage of the disease. As a therapeutic target, SGLT2 has been successfully engaged by orally active, selective agents. Initially developed as antihyperglycemic drugs, SGLT2 inhibitors have deployed a range of in vivo actions. Consequences of their primary effect, i...
May 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28502502/dapagliflozin-in-patients-with-type-ii-diabetes-mellitus-with-and-without-elevated-triglyceride-and-reduced-high-density-lipoprotein-cholesterol-levels
#12
Harold E Bays, Peter Sartipy, John Xu, Carl David Sjöström, James A Underberg
BACKGROUND: Dapagliflozin is a selective sodium-glucose cotransporter 2 inhibitor that improves glycemic control in patients with type II diabetes mellitus (T2DM) by reducing renal glucose reabsorption. OBJECTIVE: The aim was to evaluate the lipid effects of dapagliflozin 10 mg or placebo in patients with T2DM with/without baseline elevated triglyceride and reduced high-density lipoprotein (HDL) cholesterol levels. METHODS: This was a post hoc analysis of 10 phase 3, placebo-controlled studies of dapagliflozin 10 mg (N = 2237) or placebo (N = 2164) administered for 24 weeks in patients with T2DM...
March 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28496550/efficacy-and-safety-of-sglt2-inhibitors-in-reducing-glycated-hemoglobin-and-weight-in-emirati-patients-with-type-2-diabetes
#13
Alaaeldin Bashier, Azza Abdulaziz Khalifa, Fauzia Rashid, Elamin Ibrahim Abdelgadir, Amina Adil Al Qaysi, Razan Ali, Ahmed Eltinay, Jalal Nafach, Fatima Alsayyah, Fatheya Alawadi
BACKGROUND: SGLT2 inhibitors are a new class of drugs that act by inhibiting glucose reabsorption in the proximal renal tubules. Many trials have demonstrated their effectiveness in reducing glycated hemoglobin (HbA1c) and weight, but they have never been examined in Arab or Emirati populations. METHODS: We assessed the efficacy of SGLT2 inhibitors in reducing HbA1c and weight in our population and specifically in an Emirati cohort. We also assessed the effect on fasting blood glucose, blood pressure, lipid profile, serum creatinine, and side effects...
June 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28496544/hemodynamic-effects-of-sodium-glucose-cotransporter-2-inhibitors
#14
REVIEW
Motoaki Sano
It is widely accepted that obesity and type 2 diabetes mellitus (T2DM) increase the risk of heart failure (HF) independently of underlying coronary artery disease. The changes in myocardial structure or function associated with diabetes have been termed diabetic cardiomyopathy. Corresponding to changes in the risk factors for HF, an epidemiologic transition is underway from HF with a reduced ejection fraction to HF with a preserved ejection fraction. Hyperglycemia can damage the myocardium, even before diagnosis of diabetes, but intensive glycemic control has no impact on the risk of HF in patients with T2DM...
June 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28477418/sodium-glucose-sglt-and-glucose-glut-transporter-expression-in-the-kidney-of-type-2-diabetic-subjects
#15
Luke Norton, Christopher Shannon, Marcel Fourcaudot, Cheng Hu, Niansong Wang, Wei Ren, Jun Song, Muhammad Abdul-Ghani, Ralph A DeFronzo, Jimmy Ren, Weiping Jia
The sodium-glucose cotransporters (SGLTs) are responsible for the tubular reabsorption of filtered glucose from the kidney into the bloodstream. The inhibition of SGLT2-mediated glucose reabsorption is a novel and highly effective strategy to alleviate hyperglycemia in patients with type 2 diabetes mellitus (T2DM). However, the effectiveness of SGLT2 inhibitor therapy is diminished due, in part, to a compensatory increase in the maximum reabsorptive capacity (Tm) for glucose in patients with T2DM. We hypothesized that this increase in Tm could be explained by an increase in the tubular expression of SGLT and GLUT transporters in these patients...
May 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28472182/common-variation-in-the-sodium-glucose-cotransporter-2-gene-slc5a2-does-neither-affect-fasting-nor-glucose-suppressed-plasma-glucagon-concentrations
#16
Anna-Maria Ordelheide, Anja Böhm, Daniela Kempe-Teufel, Robert Wagner, Fausto Machicao, Martin Heni, Norbert Stefan, Andreas Fritsche, Hans-Ulrich Häring, Harald Staiger
AIM: Inhibition of sodium/glucose cotransporter 2 (SGLT2), the key transport protein in renal glucose reabsorption, promotes glucose excretion and represents a new concept in the therapy of type-2 diabetes. In addition, SGLT2 inhibition elevates circulating glucagon concentrations and enhances hepatic glucose production. Since SGLT2 is expressed in human pancreatic α-cells and regulates glucagon release, we tested whether common variants of the SGLT2 gene SLC5A2 associate with altered plasma glucagon concentrations in the fasting state and upon glucose challenge...
2017: PloS One
https://www.readbyqxmd.com/read/28447076/promising-cardiovascular-and-blood-pressure-effects-of-the-sglt2-inhibitors-a-new-class-of-antidiabetic-drugs
#17
REVIEW
S G Chrysant
Patients with type 2 diabetes mellitus (T2DM) exhibit an increased risk of cardiovascular (CV) events. Treatment of these patients with traditional as well as newer glucose-lowering drugs has not demonstrated superiority in CV outcomes compared to placebo, despite effective control of diabetes. However, the recently FDA-approved sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of T2DM have demonstrated promising CV-protecting and blood pressure-lowering effects in addition to their effectiveness in glucose lowering, making them a novel class of drugs for the treatment of T2DM...
March 2017: Drugs of Today
https://www.readbyqxmd.com/read/28431667/the-potential-and-pitfalls-of-glp-1-receptor-agonists-for-renal-protection-in-type-2-diabetes
#18
Merlin C Thomas
Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) offer substantial benefits for the management of glucose levels in type 2 diabetes. In addition, recent data from clinical trials have demonstrated that treatment with Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) are also able to reduce new onset macroalbuminuria. These benefits may be consistent with the known effects of GLP-1 RA on traditional risk factors for progressive kidney disease including glucose lowering, blood pressure lowering, reduced insulin levels and weight reduction...
April 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28428225/empagliflozin-and-kinetics-of-renal-glucose-transport-in-healthy-and-type-2-diabetic-individuals
#19
Hussein Al-Jobori, Giuseppe Daniele, Eugenio Cersosimo, Curtis Triplitt, Luke Norton, Ralph A DeFronzo, Muhammad Abdul-Ghani
Renal glucose reabsorption was measured with the stepped-hyperglycemic clamp in 15 T2DM and 15 non-diabetic subjects after 2 days and after more chronic (14 days) treatment with empagliflozin. T2DM patients had significantly greater maximal renal glucose transport (TmG) compared to nondiabetic subjects at baseline (459±53 vs 337±25 mg/min, p<0.05). Empagliflozin treatment for 48 hours reduced the TmG in both diabetic and non-diabetic individuals by 44±7% and 53±6%, respectively (both p<0.001). TmG was further reduced by empagliflozin in both groups on day 14 (by 65±5% and 75±3%, respectively)...
April 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28395380/streptozotocin-treated-high-fat-fed-mice-a-new-type-2-diabetes-model-used-to-study-canagliflozin-induced-alterations-in-lipids-and-lipoproteins
#20
Tian Yu, Mitchell J Sungelo, Ira J Goldberg, Hong Wang, Robert H Eckel
The pharmacological effects of type 2 diabetes (T2DM) medications on lipoprotein metabolism are difficult to assess in preclinical models because those created failure to replicate the human condition in which insulin deficiency is superimposed on obesity-related insulin resistance. To create a better model, we fed mice with high fat (HF) diet and treated the animals with low dose streptozotocin (STZ) to mimic T2DM. We used this model to evaluate the effects of canagliflozin (CANA), a drug that reduces plasma glucose by inhibiting the sodium-glucose transporter 2 (SGLT2), which mediates ~90% of renal glucose reabsorption] on lipid and lipoprotein metabolism...
May 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
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