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Nelson Andrade, Cláudia Silva, Fátima Martel
The pathogenesis of various gastrointestinal diseases, including gastrointestinal cancers and inflammatory bowel disease, is associated with increased oxidative stress levels. We aimed to investigate the effect of oxidative stress induced by tert -butylhydroperoxide (TBH) on the uptake of 3 H-deoxy-d-glucose (3 H-DG) and 14 C-fructose by the human intestinal Caco-2 cell line. TBH (500 μM; 24 h) increased lipid peroxidation (TBARS) levels and was not cytotoxic. TBH (500 μM; 24 h) increased uptake of both low (SGLT1-mediated) and high concentrations (SGLT1- and GLUT2-mediated) of 3 H-DG, but did not affect absorption of 14 C-fructose (GLUT2- and GLUT5-mediated)...
November 1, 2018: Toxicology Research
Hwee-Yeong Ng, Yueh-Ting Lee, Wei-Hung Kuo, Pei-Chen Huang, Wei-Chia Lee, Chien-Te Lee
BACKGROUND/AIMS: Hyperglycemia and hyperuricemia are two major disorders of Metabolic syndrome. Kidney plays a crucial role in maintaining the homeostasis of uric acid and glucose. The aim of the study was to examine the changes of renal glucose and uric acid transporters in animals with metabolic syndrome. METHODS: Sprague-Dawley rats were fed with high fructose diet (60%) for 3 months (FR-3) and 5 months (FR-5). At the end study, serum and urine biochemical data were compared...
December 7, 2018: Kidney & Blood Pressure Research
Paola Bisignano, Chiara Ghezzi, Hyunil Jo, Nicholas F Polizzi, Thorsten Althoff, Chakrapani Kalyanaraman, Rosmarie Friemann, Matthew P Jacobson, Ernest M Wright, Michael Grabe
Sodium-dependent glucose transporters (SGLTs) exploit sodium gradients to transport sugars across the plasma membrane. Due to their role in renal sugar reabsorption, SGLTs are targets for the treatment of type 2 diabetes. Current therapeutics are phlorizin derivatives that contain a sugar moiety bound to an aromatic aglycon tail. Here, we develop structural models of human SGLT1/2 in complex with inhibitors by combining computational and functional studies. Inhibitors bind with the sugar moiety in the sugar pocket and the aglycon tail in the extracellular vestibule...
December 7, 2018: Nature Communications
Raja Rezg, Anne Abot, Bessem Mornagui, Claude Knauf
Bisphenol S, an industrial chemical, has raised concerns for both human and ecosystem health. Yet, health hazards posed by bisphenol S (BPS) exposure remain poorly studied. Compared to all tissues, the intestine and the liver are among the most affected by environmental endocrine disruptors. The aim of this study was to investigate the molecular effect of BPS on gene expression implicated in the control of glucose metabolism in the intestine (apelin and its receptor APJ, SGLT1, GLUT2) and in the liver (glycogenolysis and/or gluconeogenesis key enzymes (glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK)) and pro-inflammatory cytokine expression (TNF-α and IL-1β))...
December 7, 2018: Environmental Science and Pollution Research International
Blythe D Shepard, Hermann Koepsell, Jennifer L Pluznick
Olfactory receptors (ORs) are G protein-coupled receptors which serve to detect odorants in the nose. Additionally, these receptors are expressed in other tissues where they have functions outside of the canonical smell response. Olfactory Receptor 1393 (Olfr1393) was recently identified as a novel regulator of sodium glucose co-transporter 1 (Sglt1) localization in the renal proximal tubule. Glucose reabsorption in the proximal tubule (via Sglt1 and Sglt2) has emerged as an important contributor to the development of diabetes...
November 28, 2018: American Journal of Physiology. Renal Physiology
Ken Lee Chin, Richard Ofori-Asenso, Ingrid Hopper, Thomas G von Lueder, Christopher M Reid, Sophia Zoungas, Bing H Wang, Danny Liew
There is growing evidence from phase III randomised clinical trials of the cardiovascular benefits of sodium glucose cotransporter 2 (SGLT2) inhibitors in patients with diabetes mellitus. It is hypothesised that these benefits are mediated by mechanisms other than glucose control. To address this, we performed a systematic review of data from preclinical studies examining the direct cardioprotective effects of SGLT2 inhibitors. Medline, EMBASE, CINAHL and International Pharmaceutical Abstracts databases were searched for preclinical studies that examined the potential cardioprotective effects of SGLT2 inhibitors...
November 26, 2018: Cardiovascular Research
Yunyun Li, Xiaoxi Lu, Haiqin Wu, Mi Xia, Qihang Hou, Weiwei Hu, Tiejun Li, Li Wu, Qinghua Yu
To explore the effects of reducing the Cp levels on intestinal barrier function, low Cp (LP) and NRC standard Cp (NP) diets were fed to pigs from 45 to 160 days, and in vitro experiments were performed using monolayers of IPEC-J2 cells. The number of goblet cells, expression of proteins related to cell junction, amino acid transport, glucose transport, transepithelial electrical resistance (TEER), dextran permeability, and IL-6 secretion level were detected in pigs. The results demonstrated that a moderate reduction of Cp levels did not affect intestinal morphology, as demonstrated by a normal villi height, crypt depth and normal numbers of goblet cells...
November 12, 2018: Research in Veterinary Science
Aleksandra Novikov, Yiling Fu, Winnie Huang, Brent Freeman, Rohit Patel, Charlotte van Ginkel, Hermann Koepsell, Meinrad Busslinger, Akira Onishi, Josselin Nespoux, Volker Vallon
Inhibitors of the sodium-glucose cotransporter SGLT2 enhance urinary glucose and urate excretion and lower plasma urate levels. The mechanisms remain unclear, but a role for enhanced glucose in the tubular fluid has been proposed, which may interact with tubular urate transporters like GLUT9 or URAT1. Studies were performed in non-diabetic mice using the SGLT2 inhibitor canagliflozin and gene targeted mice lacking the urate transporter GLUT9 in the tubule or mice with whole body knockout of SGLT2, SGLT1, or URAT1...
November 14, 2018: American Journal of Physiology. Renal Physiology
Andrew W Moran, Miran A Al-Rammahi, Daniel J Batchelor, David M Bravo, Soraya P Shirazi-Beechey
The Na+ /glucose cotransporter 1, SGLT1 is the major route for transport of dietary glucose from the lumen of the intestine into absorptive enterocytes. Sensing of dietary sugars and artificial sweeteners by the sweet taste receptor, T1R2-T1R3, expressed in the enteroendocrine L-cell regulates SGLT1 expression in neighboring absorptive enterocytes. However, the mechanism by which sugar sensing by the enteroendocrine cell is communicated to the absorptive enterocytes is not known. Here, we show that glucagon-like peptide-2 (GLP-2) secreted from the enteroendocrine cell in response to luminal sugars regulates SGLT1 mRNA and protein expression in absorptive enterocytes, via the enteric neurons...
2018: Frontiers in Nutrition
Takayoshi Suga, Osamu Kikuchi, Masaki Kobayashi, Sho Matsui, Hiromi Yokota-Hashimoto, Eri Wada, Daisuke Kohno, Tsutomu Sasaki, Kazusane Takeuchi, Satoru Kakizaki, Masanobu Yamada, Tadahiro Kitamura
OBJECTIVES: It is controversial whether sodium glucose transporter (SGLT) 2 inhibitors increase glucagon secretion via direct inhibition of SGLT2 in pancreatic α cells. The role of SGLT1 in α cells is also unclear. We aimed to elucidate these points that are important not only for basic research but also for clinical insight. METHODS: Plasma glucagon levels were assessed in the high-fat, high-sucrose diet (HFHSD) fed C57BL/6J mice treated with dapagliflozin or canagliflozin...
October 27, 2018: Molecular Metabolism
Michael Morkos, Nasha K Nensey, Anila Bindal
Objective: Patients with type 1 diabetes mellitus (T1DM) are insulin-dependent. Infection increases insulin resistance and subsequently increases insulin needs. We are reporting the first case of a patient with T1DM and severe infection who has reduced insulin needs after starting micafungin therapy. Methods: A 29-year-old Hispanic female with known history of long-standing uncontrolled type 1 diabetes presented for evaluation of worsening dysphagia and dyspnea...
November 5, 2018: Journal of Clinical Endocrinology and Metabolism
Nadine Schafer, Prashanth Reddy Rikkala, Maike Veyhl-Wichmann, Thorsten Keller, Christian Ferdinand Jurowich, Dietmar Geiger, Hermann Koepsell
A domain of protein RS1 ( RSC1A1 ) termed RS1-Reg downregulates plasma membrane abundance of Na+ -D-glucose cotransporter SGLT1 by blocking the exocytotic pathway at the trans -Golgi. This effect is blunted by intracellular glucose but prevails when serine in a QSP motif is replaced by glutamate (RS1-Reg(S20E)). RS1-Reg binds to ornithine decarboxylase (ODC) and inhibits ODC in a glucose-dependent manner. Because ODC inhibitor difluoromethylornithine (DFMO) acts like RS1-Reg(S20E) and DFMO and RS1-Reg(S20E) are not cumulative, we raised the hypothesis that RS1-Reg(S20E) downregulates the exocytotic pathway of SGLT1 at the trans -Golgi by inhibiting ODC...
October 24, 2018: Molecular Pharmacology
Shiyi Tian, Jue Wang, Hu Yu, Jing Wang, Weiyun Zhu
Background: Most research on galacto-oligosaccharides (GOS) has mainly focused on their prebiotic effects on the hindgut, but their beneficial effects on the small intestine (SI) have received little attention. Since jejunum is the important place to digest and absorb nutrients efficiently, optimal maturation of the jejunum is necessary for maintaining the high growth rate in the neonate. Therefore, this study investigates the effect of the early intervention with GOS on the intestinal development of the jejunum...
2018: Journal of Animal Science and Biotechnology
Mentor Sopjani, Lulzim Millaku, Dashnor Nebija, Merita Emini, Miribane Dermaku-Sopjani, Arleta Rifati-Nixha
Glycogen synthase kinase-3 (GSK-3) is a highly evolutionarily conserved and ubiquitously expressed serine/threonine kinase, an enzyme protein profoundly specific for glycogen synthase (GS). GSK-3 is involved in various cellular functions and physiological processes, including cell proliferation, differentiation, motility, and survival as well as glycogen metabolism, protein synthesis, and apoptosis. There are two isoforms of human GSK-3 (named GSK-3α and GSK-3β) encoded by two distinct genes. Recently, GSK-3β has been reported to function as a powerful regulator of various transport processes across the cell membrane...
October 9, 2018: Current Medicinal Chemistry
L X Wang, S L Yan, J Z Li, Y L Li, X Q Ding, J Yin, X Xiong, H S Yang, Y L Yin
Understanding the regulatory mechanisms of intestinal morphology and function is essential for improving postweaning growth in pigs. The objective of this study was to identify the relationships of enterocyte proliferation with intestinal villus height, crypt depth, and nutrient digestibility in piglets. Sixty-four 21-d-old weaned piglets were used. Gastrointestinal cell proliferation was evaluated via Ki-67 immunohistochemistry. Villus height and crypt depth were measured using hematoxylin and eosin (H&E)-stained sections...
October 10, 2018: Journal of Animal Science
Katharina Schreck, Matthias F Melzig
The intestinal absorption of fatty acids, glucose and fructose is part of the basic requirements for the provision of energy in the body. High access of saturated longchain fatty acids (LCFA), glucose and fructose can facilitate the development of metabolic diseases, particularly the metabolic syndrome and type-2 diabetes mellitus (T2DM). Research has been done to find substances which decelerate or inhibit intestinal resorption of these specific food components. Promising targets are the inhibition of intestinal long-chain fatty acid (FATP2, FATP4), glucose (SGLT1, GLUT2) and fructose (GLUT2, GLUT5) transporters by plant extracts and by pure substances...
October 6, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Shoichi Kuroda, Yohei Kobashi, Takahiro Oi, Hideaki Amada, Lisa Okumura-Kitajima, Fusayo Io, Koji Yamamto, Hiroyuki Kakinuma
The design and synthesis of a novel class of low-absorbable SGLT1 inhibitors are described. To achieve low absorption in the new series, we performed an optimization study based on a strategy to increase TPSA. Fortunately, the optimization of an aglycon moiety and a side chain of the distal aglycon moiety led to the identification of compound 30b as a potent and low-absorbable SGLT1 inhibitor. Compound 30b showed a desirable PK profile in Sprague-Dawley (SD) rats and a favorable glucose-lowering effect in diabetic rats...
December 1, 2018: Bioorganic & Medicinal Chemistry Letters
Kwong-Man Ng, Yee-Man Lau, Vidhu Dhandhania, Zhu-Jun Cai, Yee-Ki Lee, Wing-Hon Lai, Hung-Fat Tse, Chung-Wah Siu
Empagliflozin, a sodium-glucose co-transporter (SGLT) inhibitor, reduces heart failure and sudden cardiac death but the underlying mechanisms remain elusive. In cardiomyocytes, SGLT1 and SGLT2 expression is upregulated in diabetes mellitus, heart failure, and myocardial infarction. We hypothesise that empagliflozin exerts direct effects on cardiomyocytes that attenuate diabetic cardiomyopathy. To test this hypothesis, cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) were used to test the potential effects of empagliflozin on neutralization of cardiac dysfunction induced by diabetic-like cultures...
October 5, 2018: Scientific Reports
Ferhaan Ahmad, Zhao Li, Kamel Shibbani
No abstract text is available yet for this article.
October 9, 2018: Journal of the American College of Cardiology
Sara B Seidelmann, Elena Feofanova, Bing Yu, Nora Franceschini, Brian Claggett, Mikko Kuokkanen, Hannu Puolijoki, Tapani Ebeling, Markus Perola, Veikko Salomaa, Amil Shah, Josef Coresh, Elizabeth Selvin, Calum A MacRae, Susan Cheng, Eric Boerwinkle, Scott D Solomon
BACKGROUND: Loss-of-function mutations in the SGLT1 (sodium/glucose co-transporter-1) gene result in a rare glucose/galactose malabsorption disorder and neonatal death if untreated. In the general population, variants related to intestinal glucose absorption remain uncharacterized. OBJECTIVES: The goal of this study was to identify functional SGLT1 gene variants and characterize their clinical consequences. METHODS: Whole exome sequencing was performed in the ARIC (Atherosclerosis Risk in Communities) study participants enrolled from 4 U...
October 9, 2018: Journal of the American College of Cardiology
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