A5059677493- Ion Transport and Channel Regulation
- Diabetes Treatment and Management
- Ion channel regulation and function
- Pancreatic function and diabetes
- Amino Acid Enzymes and Metabolism
- Metabolism, Diabetes, and Cancer
- Neuroscience and Neuropharmacology Research
- Membrane-based Ion Separation Techniques
- Parathyroid Disorders and Treatments
- Photoreceptor and optogenetics research
- Nicotinic Acetylcholine Receptors Study
- Cellular transport and secretion
- Neuroscience and Neural Engineering
- Cancer, Hypoxia, and Metabolism
- Plant nutrient uptake and metabolism
- Diet, Metabolism, and Disease
- Neuroendocrine Tumor Research Advances
- Pharmacology and Obesity Treatment
- Protein Structure and Dynamics
- Protein Kinase Regulation and GTPase Signaling
- Magnesium in Health and Disease
- Genetics and Neurodevelopmental Disorders
- Microfluidic and Bio-sensing Technologies
- Drug Transport and Resistance Mechanisms
- Caveolin-1 and cellular processes
University of California, Los Angeles
2012-2017
University of Zurich
2009-2013
University of Insubria
2009
Significance Cancers require high amounts of glucose to grow and survive, dogma is that uptake facilitated by passive transporters (GLUTs). We have identified a new mechanism import into pancreatic prostate cancer cells, namely active transport mediated sodium-dependent (SGLTs). This means the specific radioactive imaging probe for SGLTs, α-methyl-4-deoxy-4-[ 18 F]fluoro- d -glucopyranoside, may be used along with positron-emission tomography diagnose stage cancers, tumors in which GLUT 2-[...
The human Na(+)-glucose cotransporter SGLT2 is expressed mainly in the kidney proximal convoluted tubule where it considered to be responsible for bulk of glucose reabsorption. Phosphorylation profiling has revealed that exists a phosphorylated state rat renal cortex, so we decided investigate regulation (hSGLT2) by protein kinases. hSGLT2 was embryonic (HEK) 293T cells, and activity measured using radiotracer whole cell patch-clamp electrophysiology assays before after activation...
Human Na(+)-D-glucose cotransporter (hSGLT) inhibitors constitute the newest class of diabetes drugs, blocking up to 50% renal glucose reabsorption in vivo. These drugs have potential for widespread use epidemic, but how they work at a molecular level is poorly understood. Here, we electrophysiological methods assess block SGLT1 and SGLT2 expressed human embryonic kidney 293T (HEK-293T) cells compared them classic SGLT inhibitor phlorizin. Dapagliflozin...
Key points Glucose transporters are central players in glucose homeostasis. There two major classes of the body, passive facilitative (GLUTs) and secondary active sodium‐coupled (SGLTs). In present study, we report use a non‐invasive imaging technique, positron emission tomography, mice aiming to evaluate role GLUTs SGLTs controlling distribution utilization. We show that most significant for uptake into brain liver, whereas important recovery kidney. This work provides further support SGLT...
Kidneys contribute to glucose homeostasis by reabsorbing filtered in the proximal tubules via sodium-glucose cotransporters (SGLTs). Reabsorption is primarily handled SGLT2, and SGLT2-specific inhibitors, including dapagliflozin, canagliflozin, empagliflozin, increase excretion lower blood levels. To resolve unanswered questions about these we developed a novel approach map distribution of functional SGLT2 proteins rodents using positron emission tomography with 4-[ 18 F]fluoro-dapagliflozin...
SGLT2 inhibitors are a new class of drugs that have been recently developed to treat type II diabetes. They lower glucose levels by inhibiting the renal Na(+)/glucose cotransporter SGLT2, thereby increasing amount excreted in urine. Pharmacodynamics studies raised questions about how these reach brush border membrane S1 and S2 segments proximal tubule: filtered glomerulus act extracellularly, or do they enter cell intracellularly? To address this question we expressed hSGLT2 HEK-293T cells...
Significance The potential energy stored in ion gradients across cell membranes drives nutrients and out of cells by cotransport proteins, e.g., uphill glucose accumulation sodium cotransporters. Insight into the mechanism has been obtained from high-resolution atomic structures transporters, but further progress requires dynamic information about substrate movements through proteins. We have used multiple long molecular-dynamic simulations electrophysiological assays to explore dynamics...
The SLC34 solute carrier family comprises the electrogenic NaPi-IIa/b and electroneutral NaPi-IIc, which display Na(+) : P(i) cotransport stoichiometries of 3 1 2 1, respectively. We previously proposed that NaPi-IIc lacks one three interaction sites hypothesised for isoforms, but, unlike NaPi-IIa/b, its substrate binding order is undetermined. By expressing in Xenopus oocytes, isotope influx efflux assays gave results consistent with being first last to bind. To further investigate...
Type IIa/b Na(+)-coupled inorganic phosphate cotransporters (NaPi-IIa/b) are considered to be exclusively Na(+) dependent. Here we show that Li(+) can substitute for as a driving cation. We expressed NaPi-IIa/b in Xenopus laevis oocytes and performed two-electrode voltage-clamp electrophysiology uptake assays investigate the effect of external on their kinetics. Replacement 50% with reduced maximum transport rate rate-limiting plateau P(i)-induced current began at less hyperpolarizing...
Voltage clamp measurements reveal important insights into the activity of membrane ion channels. While conventional voltage systems are available for laboratory studies, these instruments generally unsuitable more rugged operating environments. In this study, we present a non-invasive microfluidic system developed use under varying gravity levels. The core component is multilayer device that provides an immobilisation site Xenopus laevis oocytes on intermediate layer, and fluid electrical...
Abstract The processes controlling targeting of glucose transporters to apical and basolateral membranes polarized cells are complex not‐well understood. We have engineered SGLT 1 GLUT 4 constructs linked fluorescent proteins highlight the differences in transporter expression trafficking, real time, different cell types. Activity was assessed parallel using a FRET sensor. In COS HEK cells, distributed between plasma membrane intracellular compartments, but there little CHO cells....
Sodium glucose cotransporters (SGLTs) mediate the translocation of carbohydrates across brush border membrane different organs such as intestine, kidney, and brain. The human SGLT5 (hSGLT5), in particular, is localized kidney were it responsible for mannose fructose reabsorption from glomerular filtrate confirmed by more recent studies on hSGLT5 knockout mice. Here we characterize functional properties expressed a stable T-Rex-HEK-293 cell line using biochemical electrophysiological assays....
Glucose homeostasis is a complex mechanism that requires the interplay between different organs. The kidney plays central role in this process by re‐absorbing 99.5% of filtered glucose proximal tubules, where SGLT1 and SGLT2 use energy provided electrochemical gradient sodium to drive transport. In recent years has received much attention as target inhibition class drugs (i.e. dapagliflozin, canagliflozin) lower blood levels type II diabetes patients blocking re‐absorption tubules. present...