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Glucose reabsorption

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https://www.readbyqxmd.com/read/28511711/sglt2-inhibitors-a-novel-choice-for-the-combination-therapy-in-diabetic-kidney-disease
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28395363/natural-products-as-lead-compounds-for-sodium-glucose-cotransporter-sglt-inhibitors
#12
Wolfgang Blaschek
Glucose homeostasis is maintained by antagonistic hormones such as insulin and glucagon as well as by regulation of glucose absorption, gluconeogenesis, biosynthesis and mobilization of glycogen, glucose consumption in all tissues and glomerular filtration, and reabsorption of glucose in the kidneys. Glucose enters or leaves cells mainly with the help of two membrane integrated transporters belonging either to the family of facilitative glucose transporters (GLUTs) or to the family of sodium glucose cotransporters (SGLTs)...
April 10, 2017: Planta Medica
https://www.readbyqxmd.com/read/28393583/spotlight-on-canagliflozin-300-review-of-its-efficacy-and-an-indirect-comparison-to-other-sglt-2-inhibitors-and-long-acting-glp-1-receptor-agonists
#13
Awadhesh Kumar Singh, Ritu Singh
Both sodium-glucose co-transporter-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been consistently found to lower blood glucose, body weight and systolic blood pressure (SBP) in patients with type 2 diabetes mellitus (T2DM). While all the SGLT-2Is inhibit glucose reabsorption by blocking SGLT-2 receptor in kidney, dose-dependently, the highest licensed dose of canagliflozin 300-mg has an additional ability to inhibit SGLT-1 receptor in intestine transiently, that may lead to additional inhibition of prandial glucose absorption, unlike other approved highly selective SGLT-2Is...
June 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28357781/utility-of-baseline-serum-phosphorus-levels-for-predicting-remission-in-acromegaly-patients
#14
G Y Yalin, S Tanrikulu, N Gul, A K Uzum, F Aral, R Tanakol
PURPOSE: High GH and IGF I levels increase tubular phosphate reabsorption in patients with acromegaly. We aimed to investigate the utility of serum phosphorus levels as an indicator for predicting chance of remission in acromegaly patients. DESIGN: Fifty-one patients (n: 51; F: 24, M: 27) with diagnosis of acromegaly were included in the study. Plasma IGF-1, Phosphorus (P) and nadir GH levels on oral glucose tolerance test (OGTT) at the time of diagnosis were analysed retrospectively...
March 29, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28356283/saving-the-sweetness-renal-glucose-handling-in-health-and-disease
#15
Blythe D Shepard, Jennifer L Pluznick
Glucose homeostasis is highly controlled, and the function of the kidney plays an integral role in this process. The exquisite control of blood glucose relies, in part, on renal glucose filtration, renal glucose reabsorption and renal gluconeogenesis. Particularly critical to maintaining glucose homeostasis is the renal reabsorption of glucose; with ~162g of glucose filtered by the kidney per day, it is imperative that the kidney have the ability to efficiently reabsorb nearly 100% of this glucose back into the bloodstream...
March 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28325783/renal-handling-of-ketones-in-response-to-sodium-glucose-cotransporter-2-inhibition-in-patients-with-type-2-diabetes
#16
Ele Ferrannini, Simona Baldi, Silvia Frascerra, Brenno Astiarraga, Elisabetta Barsotti, Aldo Clerico, Elza Muscelli
OBJECTIVE: Pharmacologically induced glycosuria elicits adaptive responses in glucose homeostasis and hormone release, including decrements in plasma glucose and insulin levels, increments in glucagon release, enhanced lipolysis, and stimulation of ketogenesis, resulting in an increase in ketonemia. We aimed at assessing the renal response to these changes. RESEARCH DESIGN AND METHODS: We measured fasting and postmeal urinary excretion of glucose, β-hydroxybutyrate (β-HB), lactate, and sodium in 66 previously reported patients with type 2 diabetes and preserved renal function (estimated glomerular filtration rate ≥60 mL · min(-1) · 1...
March 21, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28299616/promise-of-sglt2-inhibitors-in-heart-failure-diabetes-and-beyond
#17
REVIEW
Pieter Martens, Chantal Mathieu, Frederik H Verbrugge
This review provides mechanistic insight in the pleiotropic effects of sodium-glucose transporter-2 (SGLT-2) inhibitors with particular interest to the pathophysiology of heart failure. The SGLT-2 inhibitor empagliflozin has recently demonstrated an unprecedented 38% reduction in cardiovascular mortality in patients with diabetes. Despite modest effects on long-term glycemic control, highly significant reductions in heart failure admissions and end-stage kidney disease were observed. SGLT-2 inhibitors are the latest approved class of glucose-lowering agents...
March 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28270062/antidiabetic-drugs-and-the-kidney
#18
Moses Elisaf, Eleftheria Tzavela, Nikolaos Karanatsis, Vasilis Tsimichodimos
OBJECTIVE: Nephropathy is among the most common and most devastating complications of diabetes mellitus. Recent data suggest that there is a multifaceted interaction between the kidney and antidiabetic drugs. Thus, the deterioration of renal function may result in important changes in the pharmacokinetic and pharmacodynamic properties of glucose-lowering compounds. Additionally, drugs that exert their antidiabetic properties through the inhibition of proximal glucose reabsorption are now available whereas accumulating evidence suggests that some of these drugs may exert renoprotective properties that are independent of their effect on carbohydrate metabolism...
March 6, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28258533/current-therapeutic-approaches-in-the-management-of-hyperglycemia-in-chronic-renal-disease
#19
REVIEW
Vishnu Garla, Licy Yanes-Cardozo, Lillian F Lien
Diabetes mellitus (DM) and chronic kidney disease (CKD) are intricately intertwined. DM is the most common cause of CKD. Adequate control of DM is necessary for prevention of progression of CKD, while careful management of the metabolic abnormalities in CKD will assist in achieving better control of DM. Two of the key organs involved in glucose production are the kidney and the liver. Furthermore, the kidney also plays a role in glucose filtration and reabsorption. In CKD, monitoring of glycemic control using traditional methods such as Hemoglobin A1c (Hba1c) must be done with caution secondary to associated hematological abnormalities in CKD...
March 2017: Reviews in Endocrine & Metabolic Disorders
https://www.readbyqxmd.com/read/28255241/an-evidence-based-practice-oriented-review-focusing-on-canagliflozin-in-the-management-of-type-2-diabetes
#20
REVIEW
Joseph A Messana, Stanley S Schwartz, Raymond R Townsend
Caring for patients with type 2 diabetes mellitus (T2DM) has entered an era with many recent additions to the regimens used to clinically control their hyperglycemia. The most recent class of agents approved by the Food and Drug Administration (FDA) for T2DM is the sodium-glucose-linked transporter type 2 (SGLT2) inhibitors, which work principally in the proximal tubule of the kidney to block filtered glucose reabsorption. In the few years attending this new class arrival in the market, there has been a great deal of interest generated by the novel mechanism of action of SGLT2 inhibitors and by recent large outcome trials suggesting benefit on important clinical outcomes such as death, cardiovascular disease and kidney disease progression...
2017: Vascular Health and Risk Management
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