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Glucose reabsorption

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https://www.readbyqxmd.com/read/29327406/short-and-medium-term-efficacy-of-sodium-glucose-co-transporter-2-sglt-2-inhibitors-a-meta-analysis-of-randomized-clinical-trials
#1
Matteo Monami, Francesco Liistro, Alessia Scatena, Besmir Nreu, Edoardo Mannucci
AIMS: Sodium glucose co-transport-2 (SGLT-2) inhibitors reduce tubular glucose reabsorption, producing a reduction of blood glucose without stimulating insulin release. Aim of this meta-analysis is the systematic collection of available data from randomized trials, in order to establish the durability of the efficacy of SGLT-2 inhibitors on glycemic control and body mass index. METHODS: A meta-analysis was performed including all trials with a duration of at least 12 weeks, comparing SGLT-2 inhibitors with a non-SGLT-2 inhibitor agents in type 2 diabetes...
January 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29301520/sglt-2-inhibition-with-dapagliflozin-reduces-tissue-sodium-content-a-randomised-controlled-trial
#2
M V Karg, A Bosch, D Kannenkeril, K Striepe, C Ott, M P Schneider, F Boemke-Zelch, P Linz, A M Nagel, J Titze, M Uder, R E Schmieder
BACKGROUND AND AIMS: Sodium tissue content by 23Na magnetic resonance imaging (Na-MRI) has been validated in experimental and human studies. SGLT-2 inhibition blocks the reabsorption of glucose and of sodium in the proximal tubular cells in a 1:1 fashion. We hypothesized that SGLT-2 inhibition in patients with type 2 diabetes characterized by sodium retention leads to decreased tissue sodium content due to its pharmacological action. MATERIALS AND METHODS: In a prospective double blind, placebo controlled, cross-over trial 59 patients (61 ± 7...
January 4, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29300875/influence-of-genotype-floral-stage-and-water-stress-on-floral-nectar-yield-and-composition-of-m%C3%A4-nuka-leptospermum-scoparium
#3
Michael J Clearwater, Maria Revell, Stevie Noe, Merilyn Manley-Harris
Background and Aims: Floral nectar can be variable in composition, influencing pollinator behaviour and the composition of honey derived from it. The non-peroxide antibacterial activity of mānuka (Leptospermum scoparium, Myrtaceae) honey results from the chemical conversion of the triose sugar dihydroxyacetone (DHA), after DHA accumulates for an unknown reason in the nectar. This study examined variation in nectar DHA, glucose, fructose and sucrose content with floral stage of development, between mānuka genotypes with differing flower morphology, and in response to water stress...
January 2, 2018: Annals of Botany
https://www.readbyqxmd.com/read/29278293/green-tea-polyphenol-egcg-alleviates-metabolic-abnormality-and-fatty-liver-by-decreasing-bile-acid-and-lipid-absorption-in-mice
#4
Jinbao Huang, Simin Feng, Anna Liu, Zhuqing Dai, Hong Wang, Kenneth Reuhl, Wenyun Lu, Chung S Yang
SCOPE: The tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been shown to ameliorate metabolic abnormalities and fatty liver. The present study investigated the mechanisms of actions of EGCG on bile acid homeostasis and lipid metabolism. METHODS: Male C57BL/6J mice were fed a low-fat diet, a high-fat western-style diet or a high-fat western-style diet containing 0.32% EGCG. The effects of the treatments on biochemical parameters, gene expression and lipidomics were analyzed...
December 26, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29251772/population-pharmacokinetic-pharmacodynamic-analysis-to-characterize-the-effect-of-empagliflozin-on-renal-glucose-threshold-in-patients-with-type-1-diabetes-mellitus
#5
John Mondick, Matthew Riggs, Stefan Kaspers, Nima Soleymanlou, Jan Marquard, Valerie Nock
Sodium glucose cotransporter 2 inhibitors increase urinary glucose excretion (UGE) by lowering the renal threshold for glucose (RTG ). We aimed to quantify the effect of the sodium glucose cotransporter inhibitor empagliflozin on renal glucose reabsorption in patients with type 1 diabetes mellitus (T1DM) using a mechanistic population pharmacokinetic-pharmacodynamic (PK-PD) model and to compare results with analyses in patients with type 2 diabetes mellitus (T2DM). The PK-PD model was developed using data from a randomized phase 2 study in which patients with T1DM received oral once-daily empagliflozin 2...
December 18, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29246027/recent-advances-on-uric-acid-transporters
#6
REVIEW
Liuqing Xu, Yingfeng Shi, Shougang Zhuang, Na Liu
Uric acid is the product of purine metabolism and its increased levels result in hyperuricemia. A number of epidemiological reports link hyperuricemia with multiple disorders, such as kidney diseases, cardiovascular diseases and diabetes. Recent studies also showed that expression and functional changes of urate transporters are associated with hyperuricemia. Uric acid transporters are divided into two categories: urate reabsorption transporters, including urate anion transporter 1 (URAT1), organic anion transporter 4 (OAT4) and glucose transporter 9 (GLUT9), and urate excretion transporetrs, including OAT1, OAT3, urate transporter (UAT), multidrug resistance protein 4 (MRP4/ABCC4), ABCG-2 and sodium-dependent phosphate transport protein...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29241374/pharmacokinetic-drug-evaluation-of-empagliflozin-plus-linagliptin-for-the-treatment-of-type-2-diabetes
#7
Christos V Rizos, Theodosios D Filippatos, Moses S Elisaf
Type 2 diabetes mellitus has become a growing epidemic and therefore efficient treatment strategies that target its management are needed. The treatment of diabetic patients often requires the combination of antidiabetic drug classes. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) block glucose reabsorption in the proximal renal tubules. Dipeptidyl peptidase-4 inhibitors (DPP-4i) improve glucose metabolism by blocking the enzyme that degrades incretins leading to increased insulin secretion. Areas covered: The aim of the review is to present the available data on pharmacokinetic properties/pharmacodynamics, metabolic and cardiovascular effects of empagliflozin plus linagliptin combination...
December 19, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29216560/identification-of-an-oxime-containing-c-glucosylarene-as-a-potential-inhibitor-of-sodium-dependent-glucose-co-transporter-2
#8
Mao-Chia Yuan, Teng-Kuang Yeh, Chiung-Tong Chen, Jen-Shin Song, Yu-Chen Huang, Tsung-Chih Hsieh, Chung-Yu Huang, Yu-Ling Huang, Min-Hsien Wang, Szu-Huei Wu, Chun-Hsu Yao, Yu-Sheng Chao, Jinq-Chyi Lee
Treatment of hyperglycemia with drugs that block renal glucose reabsorption via inhibition of sodium-dependent glucose cotransporter 2 (SGLT2) is a novel approach to diabetes management. In this study, twenty-seven aryl C-glycosides bearing a C=N/C-N linkage at the glucosyl C6 position were designed, synthesized and evaluated for their inhibitory activity against human SGLT2 (hSGLT2). Compounds with good hSGLT2 inhibition were further investigated to determine their selectivity over hSGLT1. Of these, five representative aryl C-glycosides were chosen for pharmacokinetic analysis...
November 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29211300/fluorine-directed-glycosylation-enables-the-stereocontrolled-synthesis-of-selective-sglt2-inhibitors-for-type-ii-diabetes
#9
Anna Sadurní, Gerald Kehr, Marie Ahlqvist, Helena Peilot Sjögren, Cecilia Kankkonen, Laurent Knerr, Ryan Gilmour
Inhibition of the sodium-glucose co-transporters (SGLT1 and SGLT2) is a validated strategy to address the increasing prevalence of type II diabetes mellitus. However, achieving selective inhibition of human SGLT1 or SGLT2 remains challenging. Orally available small molecule drugs based on the D-glucose core of the natural product Gliflozin have proven to be clinically effective in this regard, effectively impeding glucose reabsorption. Herein, we disclose the influence of molecular editing with fluorine at the C2 position of the pyranose ring of Phlorizin analogues Remogliflozin Etabonate and Dapagliflozin (Farxiga®) to concurrently direct β-selective glycosylation, as is required for biological efficacy, and enhance aspects of the physicochemical profile...
December 6, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29205334/sodium-glucose-cotransporter-2-inhibitor-canagliflozin-attenuates-liver-cancer-cell-growth-and-angiogenic-activity-by-inhibiting-glucose-uptake
#10
Kosuke Kaji, Norihisa Nishimura, Kenichiro Seki, Shinya Sato, Soichiro Saikawa, Keisuke Nakanishi, Masanori Furukawa, Hideto Kawaratani, Mitsuteru Kitade, Kei Moriya, Tadashi Namisaki, Hitoshi Yoshiji
Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules. Although a recent report demonstrated the potential ability of SGLT2-Is to attenuate cancer growth of SGLT2-expressing cancer cells, little is known about the effects of SGLT2-Is on hepatocellular carcinoma (HCC). Here, we investigate the anti-cancer properties of a SGLT2-I, canagliflozin, against human liver cancer cells. SGTL2 mRNA and protein expression were detected in Huh7 and HepG2 cells, although not in HLE as well as primary human hepatocytes and hepatic stellate cells...
December 4, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29187367/oxidative-stress-increases-megalin-expression-in-the-renal-proximal-tubules-during-the-normoalbuminuric-stage-of-diabetes-mellitus
#11
Yoshifumi Kurosaki, Akemi Imoto, Fumitaka Kawakami, Masanori Yokoba, Tsuneo Takenaka, Takafumi Ichikawa, Masato Katagiri, Naohito Ishii
Megalin, an endocytic receptor expressed in proximal tubule cells, plays a critical role in renal tubular protein reabsorption and is associated with in the albuminuria observed in diabetic nephropathy. We have previously reported increased oxidant production in the renal cortex during the normoalbuminuric stage of diabetes mellitus (DM); however, the relationship between oxidative stress and renal megalin expression during the normoalbuminuric stage of DM remains unclear. In the present study, we evaluated whether oxidative stress affects megalin expression in the normoalbuminuric stage of DM in a streptozotocin-induced diabetic rat model and in immortalized human proximal tubular cells (HK-2)...
November 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29177922/sglt1-and-sglt1-inhibitors-a-role-to-be-assessed-in-the-current-clinical-practice
#12
Leonardo Spatola, Silvia Finazzi, Claudio Angelini, Marco Dauriz, Salvatore Badalamenti
Diabetes is a complex disease of increasingly common occurrence worldwide. Attaining optimal glycemic control is the main challenge to prevent the development of diabetes-related complications and/or to stop their progression. In recent years, the pharmacologic toolkit for the treatment of diabetes has considerably expanded, thus paving the way to more pathophysiology-oriented therapies. For instance, the sodium-glucose cotransporters SGLT2 and SGLT1 have been in the spotlight because of better knowledge of their physiology and therapeutic potential...
November 24, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29169037/a-nephron-model-for-study-of-drug-induced-acute-kidney-injury-and-assessment-of-drug-induced-nephrotoxicity
#13
Yueyang Qu, Fan An, Yong Luo, Yao Lu, Tingjiao Liu, Weijie Zhao, Bingcheng Lin
In this study, we developed a multilayer microfluidic device to simulate nephron, which was formed by "glomerulus", "Bowman's capsule", "proximal tubular lumen" and "peritubular capillary". In this microdevice, artificial renal blood flow was circulating and glomerular filtrate flow was single passing through, mimicking the behavior of a nephron. In this dynamic artificial nephron, we observed typical renal physiology, including the glomerular size-selective barrier, glomerular basement membrane charge-selective barrier, glucose reabsorption and para-aminohippuric acid secretion...
November 14, 2017: Biomaterials
https://www.readbyqxmd.com/read/29165885/the-association-between-the-dosage-of-sglt2-inhibitor-and-weight-reduction-in-type-2-diabetes-patients-a-meta-analysis
#14
Xiaoling Cai, Wenjia Yang, Xueying Gao, Yifei Chen, Lingli Zhou, Simin Zhang, Xueyao Han, Linong Ji
OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2) inhibitors may induce urinary glucose excretion via the inhibition of renal glucose reabsorption, improve glycemic control, and lower body weight. The aim of this meta-analysis was to evaluate weight changes in patients who received different dosages of SGLT2 inhibitors. METHODS: Overall, 55 placebo-controlled trials were included. RESULTS: The results indicated that treatment with 2.5 mg, 5 mg, 10 mg, and 20 mg of dapagliflozin led to significant decreases in body weight compared with a placebo (weighted mean difference [WMD], -1...
November 22, 2017: Obesity
https://www.readbyqxmd.com/read/29156994/experimental-diabetes-impairs-maternal-reproductive-performance-in-pregnant-wistar-rats-and-their-offspring
#15
Leticia Bequer, Tahiry Gómez, José L Molina, Alain Álvarez, Claudia Chaviano, Sonia Clapés
The aim of this study was to determine the effect of mild hyperglycemia on metabolism during pregnancy, the maternal reproductive performance, and the characteristics of the offspring in neonatal mild diabetic-induced Wistar rats. The experimental diabetes model was generated by neonatal streptozotocin administration (100 mg of streptozotocin/Kg bw/sc) in female Wistar rats. At adulthood, the control and diabetic group were mated. At the 20th day of gestation, a maternal and fetal blood sample were collected for biochemical measurement...
November 20, 2017: Systems Biology in Reproductive Medicine
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
#16
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/29114945/hyperglycaemia-induced-by-chronic-i-p-and-oral-glucose-loading-leads-to-hypertension-through-increased-na-retention-in-proximal-tubule
#17
Selim Fakhruddin, Wael A Alanazi, Hussain N Alhamami, Karen P Briski, Keith E Jackson
What is the central question of the study? Chronic glucose feeding accompanied by glucose injection (i.p.) causes sustained hyperglycaemia and hypertension in rats. The exact reason for the hypertension is not known. We explore some molecular pathways of the renal proximal tubule that might promote Na+ retention. What is the main finding and its importance? Development of hypertension was mediated by upregulation of the renal renin-angiotensin system and oxidative stress, acting via the Na+ -K+ -ATPase α1 -subunit in the proximal tubule, which appears to pump intracellular Na+ into the extracellular space, increasing Na+ reabsorption and blood pressure...
November 7, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/29109021/renal-organic-anion-transporters-in-drug-drug-interactions-and-diseases
#18
REVIEW
Xiaokui Huo, Kexin Liu
The kidney plays a vital role in maintaining systemic homeostasis. Active tubular secretion and reabsorption, which are mainly mediated by transporters, is an efficient mechanism for retaining glucose, amino acids, and other nutrients and for the clearance of endogenous waste products and xenobiotics. These substances are recognized by uptake transporters located in the basolateral and apical membranes of renal proximal tubule cells and are extracted from plasma and urine. Organic anion transporters (OATs) belong to the solute carrier (SLC) 22 superfamily and facilitate organic anions across the plasma membranes of renal proximal tubule cells...
November 8, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29108038/prepartum-daylight-exposure-increases-serum-calcium-concentrations-in-dairy-cows-at-the-onset-of-lactation
#19
R Özçelik, R M Bruckmaier, L E Hernández-Castellano
In dairy cows, hypocalcemia is caused by the sudden calcium demand by the mammary gland at the onset of lactation. Calcitriol (1,25-dihydroxy vitamin D; 1,25-VitD) increases the intestinal calcium absorption and the renal calcium reabsorption. Daylight contributes to the formation of 1,25-VitD, as it transforms 7-dehydrocholesterol into cholecalciferol, a 1,25-VitD precursor. Calving pens are usually set in quiet places where cows can stay calm and relaxed before parturition. However, those pens often have poor lighting conditions and therefore cows may become vitamin D deficient because of inadequate daylight exposure...
October 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/29081625/sodium-glucose-transporter-2-inhibitors-and-diabetic-ketoacidosis-in-three-patients-with-diabetes-underlying-causation
#20
Jordan L Kelley, Matthew Strum, Daniel M Riche, Andrew M Chandler
Sodium glucose transporter 2 inhibitors (SGLT2i) inhibit the reabsorption of glucose in the renal tubules reducing glycemia and increasing glucosuria. The increased glucosuria causes a shift in normal flora and colonization of pathogenic microorganisms leading to an increase in mycotic genital infections. Recent Food and Drug Administration reported cases of diabetic ketoacidosis (DKA) after initiation of SGLT2i probes the question of safety with such agents. The mechanisms of ketoacidosis and the breakdown of lipids are often misunderstood, and blame is placed on lack of insulin or on medications used to treat diabetes...
July 2017: Journal of Pharmacology & Pharmacotherapeutics
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