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SGLT 2

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https://www.readbyqxmd.com/read/28196866/sglt2-expression-is-increased-in-human-diabetic-nephropathy-sglt2-inhibition-decreases-renal-lipid-accumulation-inflammation-and-the-development-of-nephropathy-in-diabetic-mice
#1
Xiaoxin X Wang, Jonathan Levi, Yuhuan Luo, Komuraiah Myakala, Michal Herman-Edelstein, Liru Qiu, Dong Wang, Yingqiong Peng, Almut Grenz, Scott Lucia, Evgenia Dobrinskikh, Vivette D D'Agati, Hermann Koepsell, Jeffrey B Kopp, Avi Rosenberg, Moshe Levi
There is very limited human renal sodium gradient dependent glucose transporter protein SGLT2 mRNA and protein expression data reported in the literature. Aim 1 of this study was to determine SGLT2 mRNA and protein levels in human and animal models of diabetic nephropathy. We have found that the expression of SGLT2 mRNA and protein is increased in renal biopsies from human subjects with diabetic nephropathy. This is in contrast to db-db mice which had no changes in renal SGLT-2 protein expression. Furthermore, the effect of SGLT2 inhibition on renal lipid content and inflammation is not known...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28192456/the-flavanone-homoeriodictyol-increases-sglt-1-mediated-glucose-uptake-but-decreases-serotonin-release-in-differentiated-caco-2-cells
#2
Barbara Lieder, Julia Katharina Hoi, Ann-Katrin Holik, Katrin Geissler, Joachim Hans, Barbara Friedl, Kathrin Liszt, Gerhard E Krammer, Jakob P Ley, Veronika Somoza
Flavanoids and related polyphenols, among them hesperitin, have been shown to modulate cellular glucose transport by targeting SGLT-1 and GLUT-2 transport proteins. We aimed to investigate whether homoeriodictyol, which is structurally related to hesperitin, affects glucose uptake in differentiated Caco-2 cells as a model for the intestinal barrier. The results revealed that, in contrast to other polyphenols, the flavanon homoeriodictyol promotes glucose uptake by 29.0 ± 3.83% at a concentration of 100 μM...
2017: PloS One
https://www.readbyqxmd.com/read/28190822/phloridzin-inhibits-high-k-induced-contraction-via-the-inhibition-of-sodium-glucose-cotransporter-1-in-rat-ileum
#3
Hidenori Kanda, Takeharu Kaneda, Akira Kawaguchi, Noriyasu Sasaki, Tsuyoshi Tajima, Norimoto Urakawa, Kazumasa Shimizu, Hiroetsu Suzuki
Recent studies have shown that phloridzin, an inhibitor of sodium-glucose cotransporter (SGLT), strongly decreases high K(+)-induced contraction in phasic muscle, such as tenia coli, but slightly affects tonic muscle, such as trachea . In this study, we examined the inhibitory mechanism of phloridzin on high K(+)-induced muscle contraction in rat ileum, a phasic muscle. Phloridzin inhibited the high K(+)-induced contraction in the ileum and the aorta, and the relaxing effect of phloridzin at 1 mM in the ileum was approximately five-fold more potent than that in the aorta...
February 11, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28186710/lack-of-health-related-quality-of-life-and-patient-centred-outcome-measures-in-randomized-controlled-trials-conducted-for-diabetes-pharmacotherapy-sglt-2-receptor-inhibitors-as-an-example
#4
Pendar Farahani
BACKGROUND: Use of SGLT-2 receptor inhibitors has been associated with weight loss and a low rate of hypoglycemia in comparison to sulfonylureas. These factors may improve health-related quality of life for patients with diabetes. OBJECTIVES: To systematically explore randomized controlled trials (RCTs) involving SGLT-2 receptor inhibitors that reported health-related quality of life changes. METHODS: A systematic review of SGLT-2 receptor inhibitors clinical trials, limited to RCTs and English language, was conducted utilizing PubMed databases...
January 9, 2017: Journal of Population Therapeutics and Clinical Pharmacology
https://www.readbyqxmd.com/read/28170426/chronic-social-stress-in-pigs-impairs-intestinal-barrier-and-nutrient-transporter-function-and-alters-neuro-immune-mediator-and-receptor-expression
#5
Yihang Li, Zehe Song, Katelyn A Kerr, Adam J Moeser
Psychosocial stress is a major factor driving gastrointestinal (GI) pathophysiology and disease susceptibility in humans and animals. The mechanisms governing susceptibility to stress-induced GI disease remain poorly understood. In the present study, we investigated the influence of chronic social stress (CSS) in pigs, induced by 7 d of chronic mixing/crowding stress, on intestinal barrier and nutrient transport function, corticotropin releasing factor (CRF) signaling and immunological responses. Results from this study showed that CSS resulted in a significant impairment of ileal and colonic barrier function indicated by reduced transepithelial electrical resistance (TER) in the ileum and increased FD4 flux in the ileum (by 0...
2017: PloS One
https://www.readbyqxmd.com/read/28169086/basal-insulin-treatment-intensification-in-patients-with-type-2-diabetes-mellitus-a-comprehensive-systematic-review-of-current-options
#6
REVIEW
D Raccah
AIM: As type 2 diabetes mellitus progresses, most patients require treatment with basal insulin in combination with another agent to achieve recommended glycaemic targets. The purpose of this systematic review was to examine the evidence supporting the use of the available add-on treatments [rapid-acting insulin (RAI), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors] to basal insulin...
February 3, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28149983/role-of-the-kidney-in-type-2-diabetes-and-mechanism-of-action-of-sodium-glucose-cotransporter-2-inhibitors
#7
Matthew L Mintz
The aim of this supplement is to discuss the important role of the kidney in glucose homeostasis. It produces glucose via gluconeogenesis, it filters glucose from the blood, and reabsorbs the filtered glucose in the proximal tubule, mainly via the sodium-glucose cotransporter-2 (SGLT-2). SGLT-2 is paradoxically upregulated in individuals with type 2 diabetes (T2D), which results in increased glucose reabsorption and hyperglycemia. This core defect in the pathophysiology of T2D provides the rationale for the use of SGLT-2 inhibitors to increase urinary glucose excretion and reduce hyperglycemia in an insulin-independent manner...
December 2016: Journal of Family Practice
https://www.readbyqxmd.com/read/28144158/following-the-results-of-the-empa-reg-outcome-trial-with-empagliflozin-is-it-possible-to-speak-of-a-class-effect
#8
Francisco Javier Ampudia-Blasco, Irene Romera, Bernat Ariño, Ramón Gomis
BACKGROUND: The recently published cardiovascular outcomes data for the first sodium-glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, have shown cardiovascular safety and additional benefits in patients with type 2 diabetes and established cardiovascular disease. Empagliflozin showed lower rates of death from cardiovascular causes or from any causes and lower hospitalization rates from heart failure compared with placebo, both in addition to standard care. This commentary discusses the existence of a possible class effect considering the available evidence described for other SGLT2 inhibitors...
2017: International Journal of General Medicine
https://www.readbyqxmd.com/read/28128227/sodium-myoinositol-cotransporter-1-smit1-mediates-the-production-of-reactive-oxygen-species-induced-by-hyperglycemia-in-the-heart
#9
Anne Van Steenbergen, Magali Balteau, Audrey Ginion, Laura Ferté, Sylvain Battault, Christophe de Meester de Ravenstein, Jean-Luc Balligand, Evangelos-Panagiotis Daskalopoulos, Patrick Gilon, Florin Despa, Sanda Despa, Jean-Louis Vanoverschelde, Sandrine Horman, Hermann Koepsell, Gerard Berry, Louis Hue, Luc Bertrand, Christophe Beauloye
Hyperglycemia (HG) stimulates the production of reactive oxygen species in the heart through activation of NADPH oxidase 2 (NOX2). This production is independent of glucose metabolism but requires sodium/glucose cotransporters (SGLT). Seven SGLT isoforms (SGLT1 to 6 and sodium-myoinositol cotransporter-1, SMIT1) are known, although their expression and function in the heart remain elusive. We investigated these 7 isoforms and found that only SGLT1 and SMIT1 were expressed in mouse, rat and human hearts. In cardiomyocytes, galactose (transported through SGLT1) did not activate NOX2...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28120716/sglt-2-inhibitors-and-cardiovascular-risk-in-diabetes-mellitus-a-comprehensive-and-critical-review-of-the-literature
#10
Konstantinos Imprialos, Charles Faselis, Chrysoula Boutari, Konstantinos Stavropoulos, Vasilios Athyros, Asterios Karagiannis, Michael Doumas
BACKGROUND: Diabetes mellitus is a major cardiovascular risk factor. Despite the vast pharmaceutical armamentarium, current therapeutic options for the treatment of type 2 diabetes mellitus were unable to provide consistent cardiovascular benefits, apart for metformin. The newest antidiabetic class of drugs, the SGLT-2 inhibitors, seem to provide significant survival benefits. The aim of this review is to present available data that will clarify whether SGLT-2 inhibitors could precipitate in reducing cardiovascular risk in diabetes mellitus...
January 24, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28120022/-cardiovascular-aspects-of-diabetes-treatment-finally-a-reason-for-cardiologists-to-be-pleased
#11
T Forst, L Plum-Mörschel, M M Weber
Cardiovascular disease significantly determines morbidity and mortality in patients with diabetes mellitus type 2. Large clinical trials in the past left controversial evidence about the effect of blood glucose-lowering treatments on cardiovascular outcomes. In 2008, the regulatory authorities defined new requirements on cardiovascular safety data for the approval of new drugs for the treatment of type 2 diabetes mellitus. Since then, numerous large safety studies have been initiated to prove cardiovascular noninferiority of new antidiabetic drugs...
January 24, 2017: Der Internist
https://www.readbyqxmd.com/read/28116795/novel-oral-glucose-lowering-drugs-compared-to-insulin-are-associated-with-lower-risk-of-all-cause-mortality-cardiovascular-events-and-severe-hypoglycemia-in-type-2-diabetes-patients
#12
Thomas Nyström, Johan Bodegard, David Nathanson, Marcus Thuresson, Anna Norhammar, Jan W Eriksson
AIMS: To investigate the association of novel oral glucose lowering drugs (GLDs) compared with insulin to risk of all-cause mortality, cardiovascular disease (CVD) and severe hypoglycaemia. METHODS: During 2013-2014 all type 2 diabetes patients in Sweden identified as new users of novel oral GLDs, i.e. either dipeptidyl-peptidase-4 inhibitors (DPP-4i) or sodium glucose cotransporter-2 inhibitors (SGLT-2i; only dapagliflozin available in Sweden during the study period), compared to insulin treatment in the Prescribed Drug Register were included and followed in the Patient- and Cause of Death Registers...
January 24, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28116097/functional-imaging-of-pharmacological-action-of-sglt2-inhibitor-ipragliflozin-via-pet-imaging-using-11-c-mdg
#13
Keisuke Mitsuoka, Yuka Hayashizaki, Yoshihiro Murakami, Toshiyuki Takasu, Masanori Yokono, Nobuhiro Umeda, Shoji Takakura, Akihiro Noda, Sosuke Miyoshi
Sodium-dependent glucose cotransporter 2 (SGLT2) is a pharmacological target of type 2 diabetes mellitus. The aim of this study was to noninvasively visualize the pharmacological action of a selective SGLT2 inhibitor ipragliflozin in the kidney using positron emission tomography (PET) imaging with (11)C-methyl-d-glucoside ((11)C-MDG), an SGLT-specific radio-labeled substrate. PET imaging with (11)C-MDG in vehicle-treated rats demonstrated that intravenously injected (11)C-MDG substantially accumulated in the renal cortex, reflecting that the compound was reabsorbed by SGLTs...
August 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28101792/medical-management-of-diabesity-do-we-have-realistic-targets
#14
REVIEW
Joseph M Pappachan, Ananth K Viswanath
PURPOSE OF REVIEW: The global prevalence of "diabesity"-diabetes related to obesity-is increasing steadily over the past few decades because of the obesity epidemic. Although bariatric surgery is an effective treatment option for patients with diabesity, its limited availability, invasiveness, relatively high costs and the potential for surgical and postsurgical complications restrict its widespread use. Therefore, medical management is the only option for a majority of patients with diabesity...
January 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28086872/dapagliflozin-decreases-small-dense-low-density-lipoprotein-cholesterol-and-increases-high-density-lipoprotein-2-cholesterol-in-patients-with-type-2-diabetes-comparison-with-sitagliptin
#15
Toshiyuki Hayashi, Tomoyasu Fukui, Noriko Nakanishi, Saki Yamamoto, Masako Tomoyasu, Anna Osamura, Makoto Ohara, Takeshi Yamamoto, Yasuki Ito, Tsutomu Hirano
BACKGROUND: The sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been reported to increase both low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol (C). This study aimed to determine how SGLT-2 inhibitors affect LDL and HDL-C subspecies. METHODS: This single center, open-label, randomized, prospective study included 80 patients with type 2 diabetes taking prescribed oral hypoglycemic agents. Patients were allocated to receive dapagliflozin (n = 40) or sitagliptin (n = 40) as add-on treatment...
January 13, 2017: Cardiovascular Diabetology
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
#16
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/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...
February 21, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28011230/sglt-2-inhibitors-their-pleiotropic-properties
#18
REVIEW
Natalia G Vallianou, Eleni Geladari, Christos E Kazazis
Type 2 diabetes mellitus has become a global pandemic. Nowadays, it is estimated that approximately 415 million people all over the world have diabetes. The sodium glucose co-transporters 2 inhibitors are a new class of glucose-lowering agents, which act through a novel mechanism by producing a decline in glucose re-absorption in the kidney, thereby increasing glycosuria and decreasing serum glucose levels. Data suggest that apart from lowering HbA1c, they produce a small but significant weight loss and a small decrease in blood pressure...
December 9, 2016: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/27995594/liraglutide-versus-sglt-2-inhibitors-in-people-with-type-2-diabetes-a-network-meta-analysis
#19
Maria Lorenzi, Uffe Jon Ploug, Jakob Langer, Rasmus Skovgaard, Michael Zoratti, Jeroen Jansen
INTRODUCTION: For people with type 2 diabetes (T2DM) inadequately controlled with oral antidiabetic drugs (OADs), evidence from both randomized controlled trials (RCTs) and real-world studies has demonstrated that treatment intensification with liraglutide offers effective glycemic control, weight reduction, and a lower risk of hypoglycemia compared to treatment intensification with insulin or additional OADs. Sodium glucose cotransporter 2 (SGLT-2) inhibitors are a new class of OADs that have also been shown to be effective in T2DM patients inadequately controlled with OADs...
February 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/27978521/the-hyperfiltering-kidney-in-diabetes
#20
Roberto Trevisan, Alessandro Roberto Dodesini
Hyperfiltering kidney is a typical feature of diabetes. Improvement observed with regard to glucose control and blood pressure control reduces the high glomerular filtration rate and may contribute to retard the appearance and the progression of diabetic renal disease. Although the mechanism of hyperfiltration is still unclear, there is mounting evidence that the increased reabsorption of glucose and sodium by sodium glucose transporter-2 (SGLT-2) is involved in this altered renal function. There is a possibility that SGLT-2 inhibition may correct hyperfiltration in diabetes, adding a new therapeutic approach to halt renal disease in patients with diabetes...
December 16, 2016: Nephron
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