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https://www.readbyqxmd.com/read/28299616/promise-of-sglt2-inhibitors-in-heart-failure-diabetes-and-beyond
#1
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/28295962/improving-glycemic-control-in-type-2-diabetes-stimulate-insulin-secretion-or-provide-beta-cell-rest
#2
REVIEW
Daniël H van Raalte, C Bruce Verchere
Type 2 diabetes (T2D) is characterized by a gradual decline of pancreatic beta cell function that determines the progressive course of the disease. While beta-cell failure is an important contributor to hyperglycemia, chronic hyperglycemia itself is also detrimental for beta-cell function, likely by inducing prolonged secretory stress on the beta cell as well as through direct glucotoxic mechanisms that have not been fully defined. For years, research has been carried out in search of therapies targeting hyperglycemia that preserve long-term beta-cell function in T2D, a quest that is still ongoing...
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28295491/national-trends-in-the-treatment-of-diabetic-nephropathy-in-the-united-states
#3
O Ajiboye, J B Segal
WHAT IS KNOWN AND OBJECTIVE: The prevalence of diabetic nephropathy continues to rise and it remains a strong predictor of morbidity and mortality in diabetic patients. Patients diagnosed with diabetic nephropathy are actively excluded from most trials involving diabetic medications and it is important to understand the prescription patterns in this subset of patients with diabetes. METHODS: Using the IMS Health's National Disease and Therapeutic Index, we analysed the medication prescription patterns for six classes of medications from 2010 to 2014 among patients, 35 years or older, with diabetic nephropathy...
March 15, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28276512/the-efficacy-and-safety-of-sglt2-inhibitors-for-adjunctive-treatment-of-type-1-diabetes-a-systematic-review-and-meta-analysis
#4
Jiao Chen, Fang Fan, J Y Wang, Yang Long, C L Gao, R C Stanton, Yong Xu
To assess the efficacy and safety of the SGLT-2 inhibitors as adjunct therapy to insulin in T1DM, clinical trials indexed in PubMed, Cochrane Library, EMbase from inception through April 5, 2016. A meta-analysis was conducted on trials of SGLT-2 inhibitors in patients with T1DM on insulin therapy using RevMan 5.3 software. Of the 371 articles identified, ten met eligibility criteria. Seven clinical trials including four randomized controlled trials and 581 patients were included. Compared with the control group, SGLT-2 inhibitors group had significantly reduced fasting plasma glucose by 0...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28274923/effect-of-diuretics-on-renal-tubular-transport-of-calcium-and-magnesium
#5
R Todd Alexander, Henrik Dimke
Calcium (Ca2+) and Magnesium (Mg2+) reabsorption along the renal tubule is dependent on distinct trans- and paracellular pathways. Our understanding of the molecular machinery involved is increasing. Ca2+ and Mg2+ reclamation in kidney is dependent on a diverse array of proteins, which are important for both forming divalent cation permeable pores and channels, but also for generating the necessary driving forces for Ca2+ and Mg2+ transport. Alterations in these molecular constituents lead to profound effects on tubular Ca2+ and Mg2+ handling...
March 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28244288/characteristics-and-impact-factors-of-renal-threshold-for-glucose-excretion-in-patients-with-type-2-diabetes-mellitus
#6
Xiao Dan Yue, Jing Yu Wang, Xin Rong Zhang, Ju Hong Yang, Chun Yan Shan, Miao Yan Zheng, Hui Zhu Ren, Yi Zhang, Shao Hua Yang, Zhen Hong Guo, Bai Chang, Bao Cheng Chang
Sodium glucose co-transporter 2 (SGLT-2) inhibitors are newly developed but promising medicine for type 2 diabetes. However, patients with a different renal threshold for glucose excretion (RT(G)) may have a different reaction to this medicine. Therefore, the objective of this study was to investigate the characteristics of RT(G) and its impact factors in patients with type 2 diabetes mellitus (T2DM). The clinical and laboratory data of 36 healthy individuals and 168 in-hospital patients with T2DM were collected and analyzed, RT(G) was calculated using blood glucose (BG) measured by dynamic BG monitoring, urinary glucose excretion (UGE) and estimated glomerular filtration rate (eGFR)...
April 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28241438/lycium-barbarum-l-polysaccharide-lbp-reduces-glucose-uptake-via-down-regulation-of-sglt-1-in-caco2-cell
#7
Huizhen Cai, Xiaohui Yang, Qian Cai, Binbin Ren, Hongyan Qiu, Zhiqing Yao
Lycium barbarum L. polysaccharide (LBP) is prepared from Lycium barbarum L. (L. barbarum), which is a traditional Chinese medicine. LPB has been shown to have hypoglycemic effects. In order to gain some mechanistic insights on the hypoglycemic effects of LBP, we investigated the uptake of LBP and its effect on glucose absorption in the human intestinal epithelial cell line Caco2 cell. The uptake of LBP through Caco2 cell monolayer was time-dependent and was inhibited by phloridzin, a competitive inhibitor of SGLT-1...
February 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28222461/elements-for-success-in-managing-type-2-diabetes-with-sglt-2-inhibitors-individualizing-treatment-with-sglt-2-inhibitor-therapy-in-type-2-diabetes-mellitus
#8
Eden M Miller
The largely self-managed nature of type 2 diabetes mellitus (T2DM) underscores the importance of a collaborative decision-making process between patient and provider that best aligns the medication characteristics with the needs, interests, and abilities of the patient and with the treatment goals. The treatment regimen should be kept as simple as possible. This article applies these general principles to the use of sodium glucose cotransporter-2 inhibitor (SGLT-2) therapy, based on evidence from published studies and the clinical experience of the author...
February 2017: Journal of Family Practice
https://www.readbyqxmd.com/read/28222460/elements-for-success-in-managing-type-2-diabetes-with-sglt-2-inhibitors-overview-of-the-efficacy-and-safety-of-sglt-2-inhibitors-in-type-2-diabetes-mellitus
#9
Eden M Miller
Since the approval of the first sodium-glucose cotransporter-2 (SGLT-2) inhibitor by the US Food and Drug Administration (FDA) in 2013, the SGLT-2 inhibitors have assumed key roles in the management of patients with type 2 diabetes mellitus (T2DM). This review covers the safety and efficacy of these agents when used in this patient population.
February 2017: Journal of Family Practice
https://www.readbyqxmd.com/read/28222459/elements-for-success-in-managing-type-2-diabetes-with-sglt-2-inhibitors-role-of-the-kidney-in-glucose-homeostasis-implications-for-sglt-2-inhibition-in-the-treatment-of-type-2-diabetes-mellitus
#10
Eden M Miller
The focus on the kidney as a therapeutic target for the treatment of type 2 diabetes mellitus (T2DM) has led to the development of the sodium-glucose cotransporter-2 (SGLT-2) inhibitors, of which 3 are available in the United States. This article addresses the implications for SGLT-2 inhibition in the treatment of T2DM.
February 2017: Journal of Family Practice
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
#11
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
#12
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
#13
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
#14
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/28174043/sodium-influx-through-cerebral-sodium-glucose-transporter-type-1-exacerbates-the-development-of-cerebral-ischemic-neuronal-damage
#15
Yui Yamazaki, Shinichi Harada, Tetsuyuki Wada, Teruki Hagiwara, Shigeru Yoshida, Shogo Tokuyama
We recently reported that cerebral sodium-glucose transporter type 1 (SGLT-1) plays a role in exacerbation of cerebral ischemia. However, the mechanism by which cerebral SGLT-1 acts remains unclear. Here we demonstrated that sodium influx through cerebral SGLT-1 exacerbates cerebral ischemic neuronal damage. SGLT-specific sodium ion influx was induced using α-methyl-D-glucopyranoside (α-MG). Intracellular sodium concentrations in primary cortical neurons were estimated using sodium-binding benzofuran isophthalate fluorescence...
February 4, 2017: European Journal of 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
#16
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
#17
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
#18
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
#19
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
#20
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
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