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Glucose reabsorption

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https://www.readbyqxmd.com/read/28812381/retrospective-review-of-sglt2-inhibitor-exposures-reported-to-13-poison-centers
#1
Scott E Schaeffer, Carol DesLauriers, Henry A Spiller, Alfred Aleguas, Salvador Baeza, Mark L Ryan
BACKGROUND: SGLT2 inhibitors are a new class of oral antidiabetics prescribed in the United States since 2013. They act by inhibiting reabsorption of glucose in the proximal convoluted tubule of the kidney, allowing excess glucose to be excreted. Little has been reported regarding effects of non-therapeutic exposure to this class of medication. METHODS: Retrospective records from 13 poison centers were examined for human exposures to SGLT2 inhibitors between 1st January 2013 and 31st December 2016...
August 16, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28811850/effect-of-sodium-glucose-cotransporter-2-inhibitors-with-low-sglt2-sglt1-selectivity-on-circulating-glucagon-like-peptide-1-levels-in-type-2-diabetes-mellitus
#2
REVIEW
Kohzo Takebayashi, Toshihiko Inukai
Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that improve glycemic control by inhibiting reabsorption of glucose filtered through the renal glomerulus. Use of drugs in this class has increased because of their effect of decreasing body weight and a low risk for hypoglycemia, in addition to a relatively strong glucose-lowering effect. SGLT2 inhibitors such as canagliflozin and sotagliflozin (a SGLT1/SGLT2 dual inhibitor) also have a mild or moderate intestinal and renal SGLT1 inhibitory effect because of their relatively weak selectivity for SGLT2 over SGLT1...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28769002/mechanism-based-pharmacokinetic-pharmacodynamic-modeling-of-luseogliflozin-a-sodium-glucose-co-transporter-2-inhibitor-in-japanese-patients-with-type-2-diabetes-mellitus
#3
Yoshishige Samukawa, Masaru Mutoh, Shi Chen, Nobuo Mizui
Luseogliflozin is a selective sodium glucose co-transporter 2 (SGLT2) inhibitor that reduces hyperglycemia in type 2 diabetes mellitus (T2DM) by promoting urinary glucose excretion (UGE). A clinical pharmacology study conducted in Japanese patients with T2DM confirmed dose-dependency of UGE with once-daily administration of luseogliflozin; however, the reason for sustained UGE after plasma luseogliflozin decreased was unclear. To elucidate the effect of inhibition rate constants, Kon and Koff, and to explain the sustained UGE, a pharmacokinetic-pharmacodynamic (PK-PD) model was built based on the mechanisms of glucose filtration in the glomerulus and reabsorption in the renal proximal tubule of kidney as well as the kinetics of competitive inhibition of SGLT1/2 and inhibition rate constants of SGLT2, by using UGE and plasma glucose levels and luseogliflozin concentrations...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28768320/effects-of-sodium-glucose-cotransporter-2-inhibitors-for-the-treatment-of-patients-with-heart-failure-proposal-of-a-novel-mechanism-of-action
#4
Milton Packer, Stefan D Anker, Javed Butler, Gerasimos Filippatos, Faiez Zannad
Importance: Only 1 class of glucose-lowering agents-sodium-glucose cotransporter 2 (SGLT2) inhibitors-has been reported to decrease the risk of cardiovascular events primarily by reducing the risk of the development or progression of heart failure. In a landmark trial called Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes [EMPA-REG Outcomes], long-term treatment with empagliflozin prevented fatal and nonfatal heart failure events but did not reduce the risk of myocardial infarction or stroke in diabetic patients...
August 2, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28760225/renal-safety-profile-of-sodium-glucose-cotransporter-2-inhibitors-and-other-safety-data
#5
Pablo Gómez-Fernández, Diego Fernández-García
The main effect of SGLT2 inhibitors is their glycosuric action. These drugs reverse the deleterious effect of increased glucose reabsorption by the renal tubule in persons with DM2. In terms of efficacy, SGLT2 inhibitors produce a mean HbA1c reduction of 0.8%, although higher initial HbA1c levels can show a larger decrease. In addition to these glycaemic effects, this drug class also favours weight loss and blood pressure control, without increasing hypoglycaemic episodes. Due to their insulin-independent mechanism of action, SGLT2 inhibitors can be used in monotherapy, in patients with metformin intolerance, or in combination with other glucose-lowering drugs, including insulin...
November 2016: Medicina Clínica
https://www.readbyqxmd.com/read/28760224/hemodynamic-and-renal-implications-of-sodium-glucose-cotransporter-2-inhibitors-in-type-2-diabetes-mellitus
#6
Alberto Tejedor Jorge
In DM2, there is increased expression of the proximal glucose transporter SGLT2. The increased glucose reabsorption from the urine to the proximal tubule and subsequently to the bloodstream, has three direct effects on the prognosis of patients with DM2: a) it increases the daily glucose load by raising the renal threshold for glucose, thus augmenting requirements for oral antidiabetics and insulin. This progressive increase occurs throughout the course of the disease and in parallel with the increase in renal mass (renal hypertrophy); b) because of the greater glucose reabsorption, glycosuria is lower than the level corresponding to glycaemia, decreasing the stimulus on the tubuloglomerular feedback system of the distal nephron...
November 2016: Medicina Clínica
https://www.readbyqxmd.com/read/28760221/approaching-to-dm2-through-sodium-glucose-cotransporter-2-does-it-make-sense
#7
Julián Segura
The kidney is involved in glucose homeostasis through three main mechanisms: renal gluconeogenesis, renal glucose consumption and glucose reabsorption in the proximal tubule. Glucose reabsorption is one of the most relevant physiological functions of the kidney, through which filtered glucose is fully recovered, urine is free of glucose, and calorie loss is prevented. Approximately 90% of the glucose is reabsorbed in the S1 segment of the proximal tubule, where GLUT2 and SGLT2 transporters are located, while the remaining 10% is reabsorbed in the S3 segment by SGLT1 and GLUT1 transporters...
November 2016: Medicina Clínica
https://www.readbyqxmd.com/read/28759755/the-roles-of-sodium-glucose-cotransporter-2-inhibitors-in-preventing-kidney-injury-in-diabetes
#8
REVIEW
Krit Jaikumkao, Anchalee Pongchaidecha, Varanuj Chatsudthipong, Siriporn C Chattipakorn, Nipon Chattipakorn, Anusorn Lungkaphin
Diabetic nephropathy (DN) is the leading cause of end stage renal disease (ESRD) worldwide. The early effective treatment of high plasma glucose could delay or prevent the onset of DN. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are new target treatments for ameliorating high plasma glucose and help to maintain glucose homeostasis in diabetic patients. Reduced renal glucose reabsorption by SGLT2 inhibition seems to have high potential to improve glycemic control in diabetes mellitus (DM) not only through glucose lowering but also through glucose-independent effects such as blood pressure-lowering and direct renal effects in diabetes...
July 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28749169/effects-of-sodium-glucose-cotransporter-2-inhibitors-on-serum-uric-acid-in-type-2-diabetes-mellitus
#9
Hala Ahmadieh, Sami Azar
Hyperuricemia has been linked to metabolic syndrome, cardiovascular disease, and chronic kidney disease. Hyperuricemia and type 2 diabetes mellitus were inter-related, type 2 diabetes mellitus was more at risk of having a higher serum uric acid level, and also individuals with higher serum uric acid had higher risk of developing type 2 diabetes in the future. Insulin resistance seems to play an important role in the causal relationship between metabolic syndrome, type 2 diabetes, and hyperuricemia. Oral diabetic drugs that would have additional beneficial effects on reducing serum uric acid levels are of importance...
July 27, 2017: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/28736029/protective-role-of-apelin-against-cyclosporine-induced-renal-tubular-injury-in-rats
#10
J S Kim, J W Yang, B G Han, H J Kwon, J H Kim, S O Choi
BACKGROUND: Cyclosporine (CsA) usually reduces glomerular filtration rate (GFR) but also can induce tubular injury without resulting in GFR reduction. Apelin is an endogenous ligand for the apelin receptor and has diverse physiologic roles related to hemodynamic or metabolic processes. We investigated the renoprotective role of apelin against CsA-induced tubular toxicity in rats. METHODS: Rats were given CsA (15 mg/kg/day) and/or apelin-13 (15 μg/kg/day) for 7 days via subcutaneous injection...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28724607/renal-hemodynamic-effects-of-glucagon-like-peptide-1-agonist-are-mediated-by-nitric-oxide-but-not-prostaglandin
#11
Scott Culver Thomson, Ali Kashkouli, Zhi Zhao Liu, Prabhleen Singh
The incretin hormone, glucagon like peptide-1 (GLP-1), is known for responding to dietary fat and carbohydrate. It elicits effects on pancreas, gut, and brain to stabilize blood glucose levels. We have previously reported that the GLP-1 agonist, exenatide, vasodilates the kidney and suppresses proximal reabsorption. The present study was undertaken to determine whether the renal effects of exenatide are mediated by nitric oxide (NO) and/or prostaglandins. Inulin clearance (GFR) and urine flow rate (UV) were measured in anesthetized rats before and during exenatide infusion (1 nmol/h iv)...
July 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28721687/practical-approach-to-initiating-sglt2-inhibitors-in-type-2-diabetes
#12
REVIEW
Fernando Gomez-Peralta, Cristina Abreu, Albert Lecube, Diego Bellido, Alfonso Soto, Cristóbal Morales, Miguel Brito-Sanfiel, Guillermo Umpierrez
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are an attractive novel therapeutic option for the treatment of type 2 diabetes. They block the reabsorption of filtered glucose in kidneys, mainly in proximal renal tubules, resulting in increased urinary glucose excretion and correction of the diabetes-related hyperglycemia. Beyond improving glucose control, SGLT2 inhibitors offer potential benefits by reducing body weight and blood pressure. On the basis of the efficacy demonstrated in clinical trials, SGLT2 inhibitors are recommended as second- or third-line agents for the management of patients with type 2 diabetes...
July 18, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28679589/insulin-stimulates-uric-acid-reabsorption-via-regulating-urate-transporter-1-and-atp-binding-cassette-sub-family-g-member-2
#13
Daigo Toyoki, Shigeru Shibata, Emiko Kuribayashi-Okuma, Ning Xu, Kenichi Ishizawa, Makoto Hosoyamada, Shunya Uchida
Accumulating data indicate that renal uric acid (UA) handling is altered in diabetes and by hypoglycemic agents. In addition, hyperinsulinemia is associated with hyperuricemia and hypouricosuria. However, the underlying mechanisms remain unclear. In this study, we aimed to investigate how diabetes and hypoglycemic agents alter the levels of renal UA transporters. In insulin-depleted diabetic rats with streptozotocin treatment, both UA excretion and fractional excretion of UA (FEUA) were increased, suggesting that tubular handling of UA is altered in this model...
July 5, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28676923/biochemical-and-pharmacological-role-of-a1-adenosine-receptors-and-their-modulation-as-novel-therapeutic-strategy
#14
Katia Varani, Fabrizio Vincenzi, Stefania Merighi, Stefania Gessi, Pier Andrea Borea
Adenosine, the purine nucleoside, mediates its effects through activation of four G-protein coupled adenosine receptors (ARs) named as A1, A2A, A2B and A3. In particular, A1ARs are distributed through the body, primarily inhibitory in the regulation of adenylyl cyclase activity and able to reduce the cyclic AMP levels. Considerable advances have been made in the pharmacological and molecular characterization of A1ARs, which had been proposed as targets for the discovery and drug design of antagonists, agonists and allosteric enhancers...
July 5, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28667491/sglt-2-inhibitors-in-heart-failure-implications-for-the-kidneys
#15
REVIEW
Frederik H Verbrugge, Pieter Martens, Wilfried Mullens
PURPOSE OF REVIEW: This review aims to summarize the renal effects of sodium-glucose transporter-2 (SGLT-2) inhibitors and their potential implications in heart failure pathophysiology. RECENT FINDINGS: In patients with diabetes and established atherosclerosis, the SGLT-2 inhibitor empagliflozin versus placebo significantly reduced the rate of heart failure admissions with 35%. Moreover, empagliflozin slowed kidney disease progression and reduced the need for renal replacement therapy...
August 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28639760/-euglycemic-ketoacidosis-a-complication-of-sglt2-inhibitors
#16
Aki Mizuno, Sanaz Lolachi, Alain Pernet
Sodium-glucose cotransporter 2 (SGLT2) inhibitors constitute a new category of oral antidiabetics recently indicated for the treatment of type 2 diabetes. Their mechanism of action (inhibition of renal reabsorption of glucose) and the fact that they do not induce hypoglycemia (as monotherapy) make their clinical use interesting. Various adverse events have however been reported regarding these drugs with the euglycemic ketoacidosis being the most serious. In this article we aim to review the possible mechanism of this side effect and recommendations for use of SGLT2 inhibitors by means of a case report...
May 31, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28630133/dual-regulation-of-gluconeogenesis-by-insulin-and-glucose-in-the-proximal-tubules-of-the-kidney
#17
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. Here, we found that PT-specific IRS1/2 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. On the other hand, in streptozotocin-treated mice, although insulin action was impaired in the PTs, the gluconeogenic gene expression was unexpectedly downregulated in the renal cortex, which was restored by administration of an SGLT1/2 inhibitor...
June 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28611861/effects-of-six-kinds-of-sodium-glucose-cotransporter-2-inhibitors-on-metabolic-parameters-and-summarized-effect-and-its-correlations-with-baseline-data
#18
Hidekatsu Yanai, Mariko Hakoshima, Hiroki Adachi, Akiko Kawaguchi, Yoko Waragai, Tadanao Harigae, Yoshinori Masui, Kouki Kakuta, Hidetaka Hamasaki, Hisayuki Katsuyama, Tomoko Kaga, Akahito Sako
BACKGROUND: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) blocks reabsorption of glucose by inhibiting SGLT2 in kidney, promotes the renal excretion of glucose and improves blood glucose control without requiring insulin secretion. Anti-atherosclerotic effects of SGLT2is have not been fully elucidated until today. METHODS: We retrospectively picked up patients with type 2 diabetes who had been continuously prescribed SGLT2i for 3 months or more between April 2014 and December 2016 by a chart-based analysis, and compared metabolic parameters including coronary risk factors before the SGLT2i treatment with the data at 3 and 6 months after the SGLT2i treatment started...
July 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28598954/role-of-the-sympathetic-nervous-system-in-regulation-of-the-sodium-glucose-cotransporter-2
#19
Vance B Matthews, Rosemary H Elliot, Caroline Rudnicka, Jana Hricova, Lakshini Herat, Markus P Schlaich
BACKGROUND: The sympathetic nervous system (SNS) regulates glucose metabolism in various organs including the kidneys. The sodium glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in renal proximal tubules and its inhibition has been shown to improve glucose control, cardiovascular and renal outcomes. We hypothesized that SNS-induced alterations of glucose metabolism may be mediated via regulation of SGLT2. METHOD: We used human renal proximal tubule cells to investigate the effects of noradrenaline on SGLT2 regulation...
June 8, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28596840/novel-sglt2-inhibitor-first-in-man-studies-of-antisense-compound-is-associated-with-unexpected-renal-effects
#20
Leonie van Meer, Marloes van Dongen, Matthijs Moerland, Marieke de Kam, Adam Cohen, Jacobus Burggraaf
The antisense compound ISIS 388626 selectively inhibits renal glucose reabsorption by inhibiting the sodium-glucose cotransporter-2 (SGLT2) mRNA expression. It is developed as an insulin-independent treatment approach for type 2 diabetes mellitus (T2DM). The safety, tolerability, pharmacokinetics, and pharmacodynamics after subcutaneous administration of the drug were planned to be evaluated in healthy volunteers in a single-ascending-dose study (50-400 mg) and a multiple-ascending-dose study (6 weeks; weekly doses of 50-400 mg with loading dose regimen of three doses during the first week)...
February 2017: Pharmacology Research & Perspectives
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