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https://www.readbyqxmd.com/read/29334278/a-comparative-safety-review-between-glp-1-receptor-agonists-and-sglt2-inhibitors-for-diabetes-treatment
#1
Agostino Consoli, Gloria Formoso, Maria Pompea Antonia Baldassarre, Fabrizio Febo
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile...
January 15, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29251736/pge2-ep1-receptor-inhibits-vasopressin-dependent-water-reabsorption-and-sodium-transport-in-mouse-collecting-duct
#2
Rania Nasrallah, Joseph Zimpelmann, David Eckert, Jamie Ghossein, Sean Geddes, Jean-Claude Beique, Jean-Francois Thibodeau, Chris R J Kennedy, Kevin D Burns, Richard L Hébert
PGE2 regulates glomerular hemodynamics, renin secretion, and tubular transport. This study examined the contribution of PGE2 EP1 receptors to sodium and water homeostasis. Male EP1-/- mice were bred with hypertensive TTRhRen mice (Htn) to evaluate blood pressure and kidney function at 8 weeks of age in four groups: wildtype (WT), EP1-/-, Htn, HtnEP1-/-. Blood pressure and water balance were unaffected by EP1 deletion. COX1 and mPGE2 synthase were increased and COX2 was decreased in mice lacking EP1, with increases in EP3 and reductions in EP2 and EP4 mRNA throughout the nephron...
December 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29247356/current-and-future-pharmacological-therapies-for-nafld-nash
#3
REVIEW
Yoshio Sumida, Masashi Yoneda
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and there is no approved pharmacotherapy. The efficacy of vitamin E and pioglitazone has been established in nonalcoholic steatohepatitis (NASH), a progressive form of NAFLD. GLP-1RA and SGLT2 inhibitors, which are currently approved for use in diabetes, have shown early efficacy in NASH, and also have beneficial cardiovascular or renal effects. Innovative NASH therapies include four main pathways. The first approach is targeting hepatic fat accumulation...
December 16, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29132091/effect-of-anti-diabetic-drugs-on-bone-metabolism-evidence-from-preclinical-and-clinical-studies
#4
REVIEW
Mohammad Adil, Rashid Ali Khan, Abul Kalam, Shiva Kumar Venkata, Amit Dattatraya Kandhare, Pinaki Ghosh, Manju Sharma
Diabetes mellitus is associated with abnormal bone health and an increased risk of fracture even though patients have normal or higher BMD. The mechanisms behind diabetes mellitus- induced various skeletal disorders remain unclear. Anti-diabetic drugs may have negative or positive impact on bone metabolism. For instance, thiazolidinediones increases the bone loss and risk of fracture possibly through PPARγ activation in bone marrow cells and hamper osteoblastogenesis via decreasing Runx2 transcription factor, IGF-1 and Wnt signalling pathways...
December 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29127736/liver-x-receptor-activation-inhibits-sglt2-mediated-glucose-transport-in-human-renal-proximal-tubular-cells
#5
Pattira Chonlaket, Teerasak Wongwan, Sunhapas Soodvilai
Liver X receptors (LXRs) are members of a nuclear receptor family consisting of two isoforms, LXR-α and LXR-β. They play a major role in energy metabolism including lipid and glucose metabolism. Recent studies reported LXRs regulate plasma glucose although the mechanism is still uncertain. The present study investigated whether LXR activation regulates sodium glucose cotransporter2 (SGLT2) in human renal proximal tubular cells. LXR agonists, T0901317 and GW3965, inhibited SGLT2-mediated glucose uptake in concentration-dependent manners...
November 11, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/29018938/heart-failure-with-preserved-ejection-fraction-current-management-and-future-strategies-expert-opinion-on-the-behalf-of-the-nucleus-of-the-heart-failure-working-group-of-the-german-society-of-cardiology-dkg
#6
REVIEW
Carsten Tschöpe, Christoph Birner, Michael Böhm, Oliver Bruder, Stefan Frantz, Andreas Luchner, Lars Maier, Stefan Störk, Behrouz Kherad, Ulrich Laufs
About 50% of all patients suffering from heart failure (HF) exhibit a reduced ejection fraction (EF ≤ 40%), termed HFrEF. The others may be classified into HF with midrange EF (HFmrEF 40-50%) or preserved ejection fraction (HFpEF, EF ≥ 50%). Presentation and pathophysiology of HFpEF is heterogeneous and its management remains a challenge since evidence of therapeutic benefits on outcome is scarce. Up to now, there are no therapies improving survival in patients with HFpEF. Thus, the treatment targets symptom relief, quality of life and reduction of cardiac decompensations by controlling fluid retention and managing risk factors and comorbidities...
January 2018: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/28911306/management-of-blood-pressure-and-heart-rate-in-patients-with-diabetes-mellitus
#7
Ioanna Gouni-Berthold, Ruth Hanssen, Lisa Ravarani, Heiner K Berthold
BACKGROUND: In patients with diabetes mellitus (DM) there is a clear association between blood pressure (BP) levels and macrovascular and microvascular complications. However, the BP targets that need to be achieved for optimal outcomes remain controversial. METHODS: The purpose of this narrative review is to discuss BP targets and management in patients with DM. The subject of elevated heart rate, which has been associated with mortality in many populations, and which is observed in some patients with DM will also be addressed...
2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28879786/pharmacological-management-of-type-2-diabetes-what-s-new-in-2017
#8
André J Scheen
Introduction Novelties in the management of type 2 diabetes are dominated by the commercialisation of new glucose-lowering agents, which offer alternatives to older antidiabetic medications, and by the publication of several prospective placebo-controlled outcome trials, which demonstrated not only cardiovascular safety but also cardiovascular and renal protection with some new medications. Areas covered Updates regarding the use of glucose-lowering agents are discussed from a clinical point of view. Some new viewpoints concern older antidiabetic agents such as metformin, sulfonylureas and glitazones whose benefit-risk balance has been revisited, especially in high risk patients...
September 7, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28872686/weak-bones-in-diabetes-mellitus-an-update-on-pharmaceutical-treatment-options
#9
REVIEW
Daphne P L Lin, Crispin R Dass
OBJECTIVES: Diabetes mellitus is often associated with a number of complications such as nephropathy, neuropathy, retinopathy and foot ulcers. However, weak bone is a diabetic complication that is often overlooked. Although the exact mechanism for weak bones within diabetes mellitus is unclear, studies have shown that the mechanism does differ in both type I (T1DM) and type II diabetes (T2DM). This review, however, investigates the application of mesenchymal stem cells, recombinant human bone morphogenetic protein-2, teriparatide, insulin administration and the effectiveness of a peroxisome proliferator-activated receptor-ϒ modulator, netoglitazone in the context of diabetic weak bones...
September 5, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28837785/canagliflozin-prevents-scopolamine-induced-memory-impairment-in-rats-comparison-with-galantamine-hydrobromide-action
#10
COMPARATIVE STUDY
Nadia M S Arafa, Elham H A Ali, Mohamed Kamel Hassan
Canagliflozin (CAN) is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated to improve glycemic control in adults with type 2 diabetes mellitus. There is a little information about its effect on the cholinergic system that proposed mechanism for memory improvement occurring by SGLT2 drugs. This study aimed to estimate the effect of CAN as compared to galantamine (GAL) treatments for two weeks on scopolamine hydrobromide (SCO)-induced memory dysfunction in experimental rats. Animals divided into six groups; control (CON), CAN, GAL, SCO, SCO + CAN and SCO + GAL...
November 1, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28761216/use-of-canagliflozin-in-combination-with-and-compared-to-incretin-based-therapies-in-type-2-diabetes
#11
Richard E Pratley, Eugenio Cersosimo
In Brief Sodium-glucose cotransporter 2 (SGLT2) inhibitors and incretin-based therapies (dipeptidyl peptidase-4 [DPP-4] inhibitors and glucagon-like peptide-1 [GLP-1] receptor agonists) are widely used to treat patients with type 2 diabetes. In clinical and real-world studies, canagliflozin, an SGLT2 inhibitor, has demonstrated superior A1C lowering compared to the DPP-4 inhibitor sitagliptin. Canagliflozin can also promote modest weight/fat loss and blood pressure reduction. The addition of canagliflozin to treatment regimens that include a DPP-4 inhibitor or a GLP-1 receptor agonist has been shown to further improve glycemic control, while still maintaining beneficial effects on cardiometabolic parameters such as body weight and blood pressure...
July 2017: Clinical Diabetes: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/28671791/-cardiovascular-protection-of-patients-with-type-2-diabetes-from-empa-reg-outcome-to-leader
#12
André J Scheen, Caroline Wallemacq, Bernard Jandrain, Philippe Ernest
Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, an inhibitor of sodium-glucose type 2 (SGLT2) cotransporters, in EMPA-REG OUTCOME, and liraglutide, an agonist of glucagon-like peptide-1 (GLP-1) receptors, in LEADER, showed a significant reduction in major cardiovascular events (- 14 and - 13 %, respectively), cardiovascular mortality (- 38 and - 22 %, respectively) and all-cause mortality (- 32 and - 15 %, respectively)...
August 24, 2016: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28665967/effects-of-canagliflozin-on-weight-loss-in-high-fat-diet-induced-obese-mice
#13
Wenjun Ji, Mei Zhao, Meng Wang, Wenhui Yan, Yuan Liu, Shuting Ren, Jun Lu, Bing Wang, Lina Chen
Canagliflozin, an inhibitor of sodium glucose co-transporter (SGLT) 2, has been shown to reduce body weight during the treatment of type 2 diabetes mellitus (T2DM). In this study, we sought to determine the role of canagliflozin in body weight loss and liver injury in obesity. C57BL/6J mice were fed a high-fat diet to simulate diet-induced obesity (DIO). Canagliflozin (15 and 60 mg/kg) was administered to DIO mice for 4 weeks. Orlistat (10 mg/kg) was used as a positive control. The body weight, liver weight, liver morphology, total cholesterol (TC) and triglyceride (TG) levels were examined...
2017: PloS One
https://www.readbyqxmd.com/read/28657399/combination-sglt2-inhibitor-and-glp-1-receptor-agonist-therapy-a-complementary-approach-to-the-treatment-of-type-2-diabetes
#14
Robert S Busch, Michael P Kane
Among persons with type 2 diabetes (t2d), the development of glucose intolerance involves dysfunction in several organs and tissues, including the muscle, liver, pancreas, kidney, gastrointestinal tract, adipose tissue, and brain. individuals with t2d typically have a number of comorbidities, including hypertension, hyperlipidemia, and being overweight or obese, and are, consequently, at high cardiovascular risk. guidelines recommend a comprehensive care strategy that includes treatment of diabetes-related complications and comorbidities beyond those related to hyperglycemia...
September 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28653148/-new-pharmacologic-therapies-for-chronic-heart-failure
#15
REVIEW
T Kempf, U Bavendiek, J Bauersachs
Heart failure is a disease with a high prevalence and incidence. New therapeutic approaches are needed to prevent the onset of heart failure and to reduce the high morbidity and mortality associated with this disease. An optimized therapy of arterial hypertension in patients with risk factors and the use of the SGLT2 inhibitor empagliflozin in type 2 diabetics are proven strategies to prevent heart failure. The therapeutic options in heart failure with preserved ejection fraction are still insufficient. In heart failure with reduced ejection fraction sacubitril/valsartan, the first approved angiotensin receptor-neprilysin inhibitor, is superior to an angiotensin converting enzyme (ACE) inhibitor...
June 26, 2017: Der Internist
https://www.readbyqxmd.com/read/28639755/-the-combination-of-glp-1-analogs-and-sglt2-inhibitors-new-perspectives
#16
Claire Ritz, Jaafar Jaafar, Jacques Philippe
Type 2 diabetes therapy has expanded considerably over the last decade. Two anti-diabetic therapeutic groups, which are GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 inhibitors (sodium-glucose co-transporter-2), have shown efficacy not only on glycemic control but also on weight and other parameters that will be detailed in this article. Cardiovascular safety studies for two of these molecules were shown for the first time to decrease overall and cardiovascular mortality. The combination of these two therapeutic classes provides a logical solution due to their different mechanisms of action...
May 31, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28637887/mitigating-cardiovascular-risk-in-type-2-diabetes-with-antidiabetes-drugs-a-review-of-principal-cardiovascular-outcome-results-of-empa-reg-outcome-leader-and-sustain-6-trials
#17
REVIEW
Sanjay Kaul
The U.S. Food and Drug Administration (FDA) issued a diabetes guidance in 2008 mandating that all new antidiabetes drugs rule out excess cardiovascular (CV) risk, defined as an upper bound of the two-sided 95% CI for major adverse CV events (MACE) of less than 1.80 preapproval and 1.30 postapproval. Over 25 large, prospective, randomized, controlled clinical trials involving nearly 195,000 subjects thus far have been completed or are ongoing in accordance with this guidance. The results of seven trials have been presented so far-three with dipeptidyl peptidase 4 inhibitors, one with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and three with glucagon-like peptide 1 receptor agonists (GLP-1 RA)...
July 2017: Diabetes Care
https://www.readbyqxmd.com/read/28630133/dual-regulation-of-gluconeogenesis-by-insulin-and-glucose-in-the-proximal-tubules-of-the-kidney
#18
Motohiro Sasaki, Takayoshi Sasako, Naoto Kubota, Yoshitaka Sakurai, Iseki Takamoto, Tetsuya Kubota, Reiko Inagi, George Seki, Moritaka Goto, Kohjiro Ueki, Masaomi Nangaku, Takahito Jomori, Takashi Kadowaki
Growing attention has been focused on the roles of the proximal tubules (PTs) of the kidney in glucose metabolism, including the mechanism of regulation of gluconeogenesis. In this study, we found that PT-specific insulin receptor substrate 1/2 double-knockout mice, established by using the newly generated sodium-glucose cotransporter 2 (SGLT2)-Cre transgenic mice, exhibited impaired insulin signaling and upregulated gluconeogenic gene expression and renal gluconeogenesis, resulting in systemic insulin resistance...
September 2017: Diabetes
https://www.readbyqxmd.com/read/28584109/dapagliflozin-suppresses-glucagon-signaling-in-rodent-models-of-diabetes
#19
May-Yun Wang, Xinxin Yu, Young Lee, Sara Kay McCorkle, Shiuhwei Chen, Jianping Li, Zhao V Wang, Jaime A Davidson, Philipp E Scherer, William L Holland, Roger H Unger, Michael G Roth
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of antidiabetic drug used for the treatment of diabetes. These drugs are thought to lower blood glucose by blocking reabsorption of glucose by SGLT2 in the proximal convoluted tubules of the kidney. To investigate the effect of inhibiting SGLT2 on pancreatic hormones, we treated perfused pancreata from rats with chemically induced diabetes with dapagliflozin and measured the response of glucagon secretion by alpha cells in response to elevated glucose...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28522196/impact-of-glucose-lowering-therapies-on-risk-of-stroke-in-type-2-diabetes
#20
REVIEW
F Bonnet, A J Scheen
Patients with type 2 diabetes (T2D) have an increased risk of stroke compared with people without diabetes. However, the effects of glucose-lowering drugs on risk of ischaemic stroke in T2D have been less extensively investigated than in coronary heart disease. Some evidence, including the UKPDS, has suggested a reduced risk of stroke with metformin, although the number of studies is limited. Inhibition of the KATP channels increases ischaemic brain lesions in animals. This is in agreement with a recent meta-analysis showing an increased risk of stroke with sulphonylureas vs...
September 2017: Diabetes & Metabolism
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