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Glucose reabsorption

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https://www.readbyqxmd.com/read/28912902/effects-of-dapagliflozin-on-body-composition-and-liver-tests-in-patients-with-nonalcoholic-steatohepatitis-associated-with-type-2-diabetes-mellitus-a-prospective-open-label-uncontrolled-study
#1
Hiroshi Tobita, Shuichi Sato, Tatsuya Miyake, Shunji Ishihara, Yoshikazu Kinoshita
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an active form of nonalcoholic fatty liver disease. Risk factors for NASH include type 2 diabetes mellitus (T2DM) and obesity. Sodium-glucose cotransporter 2 (SGLT2) inhibitors used to treat T2DM prevent glucose reabsorption in the kidney and increase glucose urinary excretion. Dapagliflozin is a potent, selective SGLT2 inhibitor that reduces hyperglycemia in patients with T2DM and has been demonstrated to reduce some complications associated with NASH in rodent models...
2017: Current Therapeutic Research, Clinical and Experimental
https://www.readbyqxmd.com/read/28870626/immunoreactivity-of-urate-transporters-glut9-and-urat1-is-located-in-epithelial-cells-of-the-choroid-plexus-of-human-brains
#2
Naoya Uemura, Ryuta Murakami, Yoichi Chiba, Ken Yanase, Ryuji Fujihara, Masato Mashima, Koichi Matsumoto, Machi Kawauchi, Gotaro Shirakami, Masaki Ueno
It has been suggested that urate plays a protective role in neurons, while hyperuricemia is correlated with atherosclerosis and cardiovascular disease. However, whether there is a system that directly transports urate into the brain remains to be clarified. In this study, the localization of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1), which are known to be representative reabsorptive urate transporters, was immunohistochemically examined in autopsied human brains. Immunoreactivity of GLUT9 was observed on the apical side of the cytoplasm of epithelial cells in the choroid plexus and in the cilia of ependymal cells of the human brain...
September 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28866383/renal-glucose-metabolism-in-normal-physiological-conditions-and-in-diabetes
#3
REVIEW
Mazen Alsahli, John E Gerich
The kidney plays an important role in glucose homeostasis via gluconeogenesis, glucose utilization, and glucose reabsorption from the renal glomerular filtrate. After an overnight fast, 20-25% of glucose released into the circulation originates from the kidneys through gluconeogenesis. In this post-absorptive state, the kidneys utilize about 10% of all glucose utilized by the body. After glucose ingestion, renal gluconeogenesis increases and accounts for approximately 60% of endogenous glucose release in the postprandial period...
August 7, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28861952/use-of-sodium-glucose-cotransporter%C3%A2-2-inhibitors-in-older-patients-with-type%C3%A2-2-diabetes-mellitus
#4
Takahiro Kambara, Rei Shibata, Hiroyuki Osanai, Yoshihito Nakashima, Hiroshi Asano, Kazuyoshi Sakai, Toyoaki Murohara, Masayoshi Ajioka
AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic agents that act on the proximal renal tubules to lower blood glucose levels by inhibiting glucose reabsorption and promoting urinary glucose excretion. The present study assessed the long-term use of SGLT2 inhibitors in older patients with diabetes. METHODS: A total of 117 older patients with type 2 diabetes who were given SGLT2 inhibitors were enrolled from April 2014 to March 2016. RESULTS: The mean age of the patients was 73...
September 1, 2017: Geriatrics & Gerontology International
https://www.readbyqxmd.com/read/28854935/distribution-of-glucose-transporters-in-renal-diseases
#5
REVIEW
Leszek Szablewski
Kidneys play an important role in glucose homeostasis. Renal gluconeogenesis prevents hypoglycemia by releasing glucose into the blood stream. Glucose homeostasis is also due, in part, to reabsorption and excretion of hexose in the kidney.Lipid bilayer of plasma membrane is impermeable for glucose, which is hydrophilic and soluble in water. Therefore, transport of glucose across the plasma membrane depends on carrier proteins expressed in the plasma membrane. In humans, there are three families of glucose transporters: GLUT proteins, sodium-dependent glucose transporters (SGLTs) and SWEET...
August 31, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28843503/cyp7a1-is-continuously-increased-with-disrupted-fxr-mediated-feedback-inhibition-in-hypercholesterolemic-tallyho-jng-mice
#6
Eun-Ah Lee, Dong-In Lee, Hee-Yoen Kim, Sung-Hoon Ahn, Hye-Rim Seong, Won Hoon Jung, Ki Young Kim, Sungsub Kim, Sang Dal Rhee
TALLYHO/Jng (TH) mice reveal hypercholesterolemia at an early age before their plasma glucose levels have increased. The increased plasma cholesterol should be related to bile acids (BAs) metabolism, because cholesterol is the precursor of BAs and BAs change cholesterol metabolism in a feedback manner. We analyzed the BAs pool size, BAs composition, and expression levels of several proteins that have key roles in BAs synthesis, excretion, and reabsorption and compared them to those of C57BL/6 (B6) mice to study BAs metabolism in TH mice...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28842746/expression-profiling-and-immunolocalization-of-na-d-glucose-cotransporter-1-in-mice-employing-knockout-mice-as-specificity-control-indicate-novel-locations-and-differences-between-mice-and-rats
#7
Ivana Vrhovac Madunić, Davorka Breljak, Dean Karaica, Hermann Koepsell, Ivan Sabolić
The expression and localization of sodium-D-glucose cotransporter SGLT1 (SLC5A1), which is involved in small intestinal glucose absorption and renal glucose reabsorption, is of high biomedical relevance because SGLT1 inhibitors are currently tested for antidiabetic therapy. In human and rat organs, detailed expression profiling of SGLT1/Sglt1 mRNA and immunolocalization of the transporter protein has been performed. Using polyspecific antibodies and preabsorption with antigenic peptide as specificity control, in several organs, different immunolocalizations of SGLT1/Sglt1 between human and rat were obtained...
August 26, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28840540/a-more-tubulocentric-view-of-diabetic-kidney-disease
#8
REVIEW
Letizia Zeni, Anthony G W Norden, Giovanni Cancarini, Robert J Unwin
Diabetic nephropathy (DN) is a common complication of Diabetes Mellitus (DM) Types 1 and 2, and prevention of end stage renal disease (ESRD) remains a major challenge. Despite its high prevalence, the pathogenesis of DN is still controversial. Initial glomerular disease manifested by hyperfiltration and loss of glomerular size and charge permselectivity may initiate a cascade of injuries, including tubulo-interstitial disease. Clinically, 'microalbuminuria' is still accepted as an early biomarker of glomerular damage, despite mounting evidence that its predictive value for DN is questionable, and findings that suggest the proximal tubule is an important link in the development of DN...
August 24, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28836175/canagliflozin-a-review-in-type-2-diabetes
#9
Emma D Deeks, André J Scheen
Canagliflozin (Invokana(®)) is a sodium-glucose co-transporter-2 (SGLT2) inhibitor indicated in various countries worldwide for the once-daily oral treatment of type 2 diabetes (T2D). Canagliflozin lowers blood glucose levels independently of insulin, with the inhibition of SGLT2 reducing renal reabsorption of glucose and increasing excretion of glucose in the urine. In well-designed clinical trials, canagliflozin (as first-line monotherapy or add-on therapy to other antihyperglycaemic agents) improved glycaemic control in adults with T2D, including those of older age and/or at high cardiovascular (CV) risk, and also had beneficial effects on their bodyweight and blood pressure (BP)...
August 23, 2017: Drugs
https://www.readbyqxmd.com/read/28821595/a-computational-model-of-1-5-ag-dynamics-during-pregnancy
#10
Seyedeh M Zekavat, Slava Butkovich, Grace J Young, David M Nathan, Danny Petrasek
The importance of 1,5-anhydroglucitol (1,5-AG) as an intermediate biomarker for diabetic pregnancy is multi-fold: (1) it serves as a reliable indicator of moderate-level glycemic control, especially during early gestation; (2) it has been associated with increased risk of diabetes, independent of HbA1c and fasting glucose; and (3) it is an independent risk factor for the development of eclampsia during pregnancy. However, the clinical use of this biomarker during pregnancy has been underutilized due to physiological changes in glomerular filtration rate, plasma volume, and other hemodynamic parameters which have been hypothesized to bias gestational serum 1,5-AG concentrations...
August 2017: Physiological Reports
https://www.readbyqxmd.com/read/28812381/retrospective-review-of-sglt2-inhibitor-exposures-reported-to-13-poison-centers
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
October 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
#19
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
#20
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
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