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Sodium glucose transport inhibitors

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https://www.readbyqxmd.com/read/29676804/the-biphasic-effect-of-extracellular-glucose-concentration-on-carbachol-induced-fluid-secretion-from-mouse-submandibular-glands
#1
Momomi Terachi, Chikara Hirono, Michinori Kitagawa, Makoto Sugita
Cholinergic agonists evoke elevations of the cytoplasmic free-calcium concentration ([Ca2+ ]i ) to stimulate fluid secretion in salivary glands. Salivary flow rates are significantly reduced in diabetic patients. However, it remains elusive how salivary secretion is impaired in diabetes. Here, we used an ex vivo submandibular gland perfusion technique to characterize the dependency of salivary flow rates on extracellular glucose concentration and activities of glucose transporters expressed in the glands. The cholinergic agonist carbachol (CCh) induced sustained fluid secretion, the rates of which were modulated by the extracellular glucose concentration in a biphasic manner...
April 20, 2018: European Journal of Oral Sciences
https://www.readbyqxmd.com/read/29674332/potent-sglt1-2-dual-inhibition-improves-glycemic-control-without-marked-gastrointestinal-adaptation-or-colonic-microbiota-changes-in-rodents
#2
Fuyong Du, Simon Hinke, Cassandre Cavanaugh, David Polidori, Nathanial Wallace, Thomas Kirchner, Matthew Jennis, Wensheng Lang, Gee-Hong Kuo, Micheal Gaul, James Lenhard, Keith Demarest, Nadim J Ajami, Yin Liang, Pamela J Hornby
The sodium/glucose cotransporters (SGLT1 and SGLT2) transport glucose across the intestinal brush border and kidney tubule. Dual SGLT1/2 inhibition could reduce hyperglycemia more than SGLT2-selective in patients with Type 2 Diabetes; however, questions remain about altered gastrointestinal (GI) luminal glucose and tolerability. Therefore, this was evaluated in slc5a1-/- mice or using a potent dual inhibitor (cmpd 8; SGLT1 Ki = 1.5±0.5nM 100 fold > potency than phlorizin; SGLT2 Ki = 0.4±0.2 nM). 13C6-glucose uptake was quantified in slc5a1 -/- mice and in isolated rat jejunum...
April 19, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29673309/sodium-glucose-co-transporter-2-inhibitors-beyond-glucose-lowering
#3
Asli F Ceylan, Sidney Y Ren
Diabetes is an important cause of morbidity and mortality in worldwide. Management of blood glucose is critical for diabetic patients since diabetes carries risk for many diseases and disorders. Although there are several antidiabetic agents in the markets for a long time, some of the agents have dose-limiting side effects, such as hypoglycemia and weight gain which limits their ability to reduce cardiovascular complications. Sodium glucose co-transporter 2 (SGLT2) inhibitors are new class of antidiabetic agents which exerts their effects insulin-independent mechanism therefore they do not cause hypoglycemia in the diabetic patients...
April 19, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29670074/recovery-from-diabetic-macular-edema-in-a-diabetic-patient-after-minimal-dose-of-a-sodium-glucose-co-transporter-2-inhibitor
#4
Hideyuki Yoshizumi, Tetsushi Ejima, Tetsuhiko Nagao, Masanori Wakisaka
BACKGROUND Diabetic macular edema (DME) causes serious visual impairments in diabetic patients. The standard treatments of DME are intra-vitreous injections of corticosteroids or anti-vascular endothelial growth factor antibodies and pan-photocoagulation. These treatments are unsatisfactory in their effects and impose considerable physical and economic burdens on the patients. CASE REPORT A 63-year-old woman was diagnosed as type 2 diabetes with retinopathy 7 years ago. Before the initiation of an SGLT2 inhibitor, the dipeptidyl peptidase-4 inhibitor, sitagliptin (50 mg daily), and metformin (250 mg dai- ly) were used for her glycemic control...
April 19, 2018: American Journal of Case Reports
https://www.readbyqxmd.com/read/29663893/sglt-2-inhibition-novel-therapeutics-for-reno-and-cardioprotection-in-diabetes-mellitus
#5
Angus Gill, Stephen P Gray, Karin A Jandeleit-Dahm, Anna M D Watson
BACKGROUND: The sodium glucose co-transporter 2 (SGLT2) is primarily located within S1 of the renal proximal tubule being responsible for approximately 90% of glucose re-uptake in the kidney. Inhibition of SGLT2 is an exciting new pharmacological approach for the reduction of blood glucose in type 2 diabetic patients via inhibition of tubular glucose reabsorption. In addition to lowering glucose, this group of drugs has shown significant cardiovascular and renal protective effects. CONCLUSION: This review aims to outline the current state of preclinical research and clinical trials for different SGLT2 inhibitors and outline some of the proposed mechanisms of action, including possible effects on sympathetic nerve activity, which may contribute to the unexpected beneficial cardiovascular and reno-protective effects of this class of compounds...
April 17, 2018: Current Diabetes Reviews
https://www.readbyqxmd.com/read/29663292/the-potential-role-of-sglt2-inhibitors-in-the-treatment-of-type-1-diabetes-mellitus
#6
Hadi Fattah, Volker Vallon
Type 1 diabetes mellitus is a difficult disease to treat due to the relative paucity of therapeutic options other than injectable insulin. The latter, however, can induce hypoglycemia, which has been linked to enhanced cardiovascular risk. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-hyperglycemic medications that do not increase the hypoglycemia risk and are US Food and Drug Administration (FDA) approved in type 2 diabetes mellitus. SGLT2 inhibitors may also be of benefit in type 1 diabetic patients, in addition to insulin, although they have not yet been approved for this indication...
April 16, 2018: Drugs
https://www.readbyqxmd.com/read/29628139/drug-repurposing-in-kidney-disease
#7
REVIEW
Usha Panchapakesan, Carol Pollock
Drug repurposing, is the re-tasking of known medications for new clinical indications. Advantages, compared to de novo drug development, include reduced cost and time to market plus the added benefit of a known pharmacokinetic and safety profiles. Suitable drug candidates are identified through serendipitous observations, data mining, or increased understanding of disease mechanisms. This review highlights drugs suited for repurposing in kidney disease. The main cause of mortality in patients with chronic kidney disease is cardiovascular disease...
April 6, 2018: Kidney International
https://www.readbyqxmd.com/read/29625780/pharmacovigilance-of-sodium-glucose-co-transporter-2-inhibitors-what-a-clinician-should-know-on-disproportionality-analysis-of-spontaneous-reporting-systems
#8
E Raschi, E Poluzzi, F Salvo, A Pariente, F De Ponti, G Marchesini, U Moretti
Sodium-glucose co-transporter-2 inhibitors (SGLT2-Is) have consistently demonstrated a clinically significant reduction of cardiovascular mortality. However, their safety in clinical practice is still incompletely characterized, and post-marketing monitoring is required considering the expected increase in clinical use. Different analyses of international spontaneous reporting systems, known as disproportionality analyses (DAs), have highlighted the occurrence of ketoacidosis, amputations, acute renal failure and skin toxicity...
March 1, 2018: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29608898/canagliflozin-protects-against-non-alcoholic-steatohepatitis-in-type-2-diabetic-rats-through-zinc-alpha-2-glycoprotein-up-regulation
#9
Soad L Kabil, Nevertyty M Mahmoud
Elevated blood glucose and insulin resistance are triggering factors for non-alcoholic steatohepatitis (NASH). We investigated the effects of the Sodium Glucose co-Transporter 2 (SGLT2) inhibitor canagliflozin on NASH development in rats with type 2 diabetes mellitus as well as the possible underlying mechanisms and for the first time the effect of canagliflozin on the hepatic zinc-α2-glycoprotein (ZAG) levels. Rats were treated with nicotinamide and streptozotocin to reduce the insulin secretory capacity then fed high fat diet for 8 weeks...
March 30, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29604389/effects-of-sodium-glucose-cotransporter-2-inhibitors-on-cardiovascular-disease-death-and-safety-outcomes-in-type-2-diabetes-a-systematic-review
#10
REVIEW
Karin Rådholm, Jason Hy Wu, Muh Geot Wong, Celine Foote, Gregory Fulcher, Kenneth W Mahaffey, Vlado Perkovic, Bruce Neal
AIM: Sodium glucose co-transporter 2 (SGLT2) inhibitors appear to protect against increased risks of cardiovascular and kidney disease in patients with type 2 diabetes but also cause some harms. Whether effects are comparable across drug class or specific to individual compounds is unclear. This meta-analysis assessed the class and individual compound effects of SGLT2 inhibition versus control on cardiovascular events, death, kidney disease and safety outcomes in patients with type 2 diabetes...
March 28, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29589183/new-diabetes-therapies-and-diabetic-kidney-disease-progression-the-role-of-sglt-2-inhibitors
#11
REVIEW
Claire C J Dekkers, Ron T Gansevoort, Hiddo J L Heerspink
PURPOSE OF REVIEW: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors have emerged as a promising drug class for the treatment of diabetic kidney disease. Developed originally as glucose-lowering drugs by enhancing urinary glucose excretion, these drugs also lower many other renal and cardiovascular risk factors such as body weight, blood pressure, albuminuria, and uric acid. Results from the EMPA-REG OUTCOME and CANVAS trials show that these salutary effects translate into a reduction in cardiovascular outcomes and have the potential to delay the progression of kidney function decline...
March 27, 2018: Current Diabetes Reports
https://www.readbyqxmd.com/read/29589153/an-exploratory-study-of-dapagliflozin-for-the-attenuation-of-albuminuria-in-patients-with-heart-failure-and-type-2-diabetes-mellitus-dapper
#12
Fumiki Yoshihara, Miki Imazu, Toshimitsu Hamasaki, Toshihisa Anzai, Satoshi Yasuda, Shin Ito, Haruko Yamamoto, Kazuhiko Hashimura, Yoshio Yasumura, Kiyoshi Mori, Masataka Watanabe, Masanori Asakura, Masafumi Kitakaze
BACKGROUND AND AIMS: Sodium-dependent glucose transporter-2 (SGLT-2) inhibitors, which are anti-diabetic drugs, reportedly decrease the incidence of cardiovascular events in high-risk patients with cardiovascular diseases, and thus chronic heart failure (CHF). SGLT-2 inhibitors also decrease albuminuria in patients with type 2 diabetes mellitus (T2D). Since albuminuria is a biomarker of not only chronic kidney disease but also cardiovascular events, we hypothesized that, among T2D patients with CHF, SGLT-2 inhibitors will decrease the extent of albuminuria and also improve CHF concomitantly...
March 28, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29588466/canagliflozin-inhibits-interleukin-1%C3%AE-stimulated-cytokine-and-chemokine-secretion-in-vascular-endothelial-cells-by-amp-activated-protein-kinase-dependent-and-independent-mechanisms
#13
Sarah J Mancini, Daria Boyd, Omar J Katwan, Anastasiya Strembitska, Tarek A Almabrouk, Simon Kennedy, Timothy M Palmer, Ian P Salt
Recent clinical trials of the hypoglycaemic sodium-glucose co-transporter-2 (SGLT2) inhibitors, which inhibit renal glucose reabsorption, have reported beneficial cardiovascular outcomes. Whether SGLT2 inhibitors directly affect cardiovascular tissues, however, remains unclear. We have previously reported that the SGLT2 inhibitor canagliflozin activates AMP-activated protein kinase (AMPK) in immortalised cell lines and murine hepatocytes. As AMPK has anti-inflammatory actions in vascular cells, we examined whether SGLT2 inhibitors attenuated inflammatory signalling in cultured human endothelial cells...
March 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29573110/sglt2-inhibitor-plus-dpp-4-inhibitor-as-combination-therapy-for-type-2-diabetes-a-systematic-review-and-meta-analysis
#14
Dandan Li, Weilong Shi, Tiansheng Wang, Huilin Tang
To assess the efficacy and safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors plus dipeptidyl peptidase-4 (DPP-4) inhibitor in patients with type 2 diabetes mellitus (T2DM), we performed a systematic review and meta-analysis of 14 randomized controlled trials (RCTs) involving 4,828 patients. Compared with DPP-4 inhibitor, SGLT2 inhibitor/DPP-4 inhibitor combination therapy was significantly associated with a decrease in glycemic control [HbA1c: -0.71%, fasting plasma glucose (FPG): -25.62 mg/dL, postprandial plasma glucose: -44...
March 23, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29572114/renal-outcomes-with-sodium-glucose-cotransporter-2-sglt2-inhibitor-dapagliflozin-in-obese-insulin-resistant-model
#15
Krit Jaikumkao, Anchalee Pongchaidecha, Nuttawud Chueakula, Laongdao Thongnak, Keerati Wanchai, Varanuj Chatsudthipong, Nipon Chattipakorn, Anusorn Lungkaphin
A growing body of evidence indicates that obesity and insulin resistance contribute to the progression of renal disease. This study was performed to determine the effects of dapagliflozin, a novel sodium glucose cotransporter 2 (SGLT2) inhibitor, on renal and renal organic anion transporter 3 (Oat3) functions in high-fat diet fed rats, a model of obese insulin-resistance. Twenty-four male Wistar rats were divided into two groups, and received either a normal diet (ND) (n = 6) or a high-fat diet (HFD) (n = 18) for 16 weeks...
March 20, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29569427/sodium-glucose-co-transporter-2-inhibitors-and-the-risk-for-diabetic-ketoacidosis-in-patients-with-type-2-diabetes-mellitus-a-nationwide-population-based-cohort-study
#16
Young-Gun Kim, Ja Young Jeon, Seung Jin Han, Dae Jung Kim, Kwan-Woo Lee, Hae Jin Kim
AIMS: The risk for diabetic ketoacidosis (DKA) associated with sodium-glucose co-transporter-2 inhibitor (SGLT-2i) treatment has not been established. Thus, we aimed to estimate the risk for DKA associated with SGLT-2i treatment compared to that with dipeptidyl-peptidase IV inhibitor (DPP-4i) treatment. METHODS: A nationwide population-based cohort study using claims data of the Korean Health Insurance Review and Assessment Service from January 1, 2013 to June 30, 2017 was performed...
March 22, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29569378/rates-of-myocardial-infarction-and-stroke-in-patients-initiated-on-sglt2-inhibitors-versus-other-glucose-lowering-agents-in-real-world-clinical-practice-results-from-the-cvd-real-study
#17
Mikhail Kosiborod, Kåre I Birkeland, Matthew A Cavender, Alex Z Fu, John P Wilding, Kamlesh Khunti, Reinhard W Holl, Anna Norhammar, Marit Eika Jørgensen, Eric T Wittbrodt, Marcus Thuresson, Johan Bodegård, Niklas Hammar, Peter Fenici
The multinational, observational CVD-REAL study recently showed that initiation of sodium-glucose co-transporter-2 inhibitors (SGLT-2i) was associated with significantly lower rates of death and heart failure vs. other glucose-lowering drugs (oGLDs). This sub-analysis of CVD-REAL sought to determine the association between initiation of SGLT-2i vs. oGLDs and rates of myocardial infarction (MI) and stroke. Medical records, claims and national registers from the US, Sweden, Norway and Denmark were used to identify patients with T2D newly initiated on SGLT-2i (canagliflozin, dapagliflozin or empagliflozin) or oGLDs...
March 22, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29566300/are-the-effects-of-drugs-to-prevent-and-to-treat-heart-failure-always-concordant-the-statin-paradox-and-its-implications-for-understanding-the-actions-of-antidiabetic-medications
#18
REVIEW
Milton Packer
Most treatments for chronic heart failure are effective both in preventing its onset and reducing its progression. However, statins prevent the development of heart failure, but they do not decrease morbidity and mortality in those with established heart failure. This apparent discordance cannot be explained by an effect to prevent interval myocardial infarctions. Instead, it seems that the disease that statins were preventing in trials of patients with a metabolic disorder was different from the disease that they were treating in trials of chronic heart failure...
March 22, 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29558223/absorption-disposition-metabolism-and-excretion-of-14-c-mizagliflozin-a-novel-selective-sglt1-inhibitor-in-rats
#19
Hitoshi Ono, Yasunari Kojima, Hiroshi Harada, Yoshikazu Abe, Takuro Endo, Mamoru Kobayashi
1. The pharmacokinetic and metabolite profiles of mizagliflozin, a novel selective sodium glucose co-transporter 1 inhibitor designed to act only in the intestine, were investigated in rats. 2. Mizagliflozin administrated intravenously (0.3 mg/kg) and orally (3 mg/kg) declined with a short half-life (0.23 and 1.14 h, respectively). The absolute bioavailability was only 0.02%. Following intravenous administration of [14 C]mizagliflozin (0.3 mg/kg), radioactivity in plasma was also rapidly declined. Up to 24 h after oral administration of [14 C]mizagliflozin (1 mg/kg), radioactivity was recovered in the faeces (98...
March 20, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29535955/metformin-sodium-glucose-co-transporter-2-inhibitor-salutogenic-lifestyle-mimetics-in-a-tablet
#20
Sanjay Kalra, Jubbin Jacob, Manash P Baruah
Salutogenesis is an accepted approach for chronic disease management. Calorie restriction and exercise are two evidence based salutogenic interventions in diabetes treatment. Calorie restriction mimetics and exercise mimetics may be used as pharmacological tools to help manage diabetes in a sulutogenic manner. This article discusses the biochemical basis and pharmacology of metformin and sodium glucose cotransporter 2 inhibitors. It describes how a combination of these drugs can be used as a calories restriction and exercise mimetic, to help improve diabetes control...
January 2018: Indian Journal of Endocrinology and Metabolism
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