Membrane potential accelerates sugar uptake by stabilizing the outward facing conformation of the Na/glucose symporter vSGLT.

Sodium-dependent glucose transporters (SGLTs) couple a downhill Na ion gradient to actively transport sugars. Here, we investigate the impact of the membrane potential on vSGLT structure and function using sugar uptake assays, double electron-electron resonance (DEER), electrostatic calculations, and kinetic modeling. Negative membrane potentials, as present in all cell types, shift the conformational equilibrium of vSGLT towards an outward-facing conformation, leading to increased sugar transport rates.

SGLT2 Inhibitors: Physiology and Pharmacology.

SGLTs are sodium glucose transporters found on the luminal membrane of the proximal tubule, where they reabsorb some 180 g (1 mol) of glucose from the glomerular filtrate each day. The natural glucoside phlorizin completely blocks glucose reabsorption. Oral SGLT2 inhibitors are rapidly absorbed into the blood stream, where theyremain in the circulation for hours.

The Molecular Basis of Glucose Galactose Malabsorption in a Large Swedish Pedigree.

Glucose-galactose malabsorption (GGM) is due to mutations in the gene coding for the intestinal sodium glucose cotransporter SGLT1 (SLC5A1). Here we identify the rare variant Gln457Arg (Q457R) in a large pedigree of patients in the Västerbotten County in Northern Sweden with the clinical phenotype of GGM. The functional effect of the Q457R mutation was determined in protein expressed in oocytes using biophysical and biochemical methods.

Function Trumps Form in Two Sugar Symporters, and .

Active transport of sugars into bacteria occurs through symporters driven by ion gradients. is the most well-studied proton sugar symporter, whereas is the most characterized sodium sugar symporter. These are members of the major facilitator (MFS) and the amino acid-Polyamine organocation (APS) transporter superfamilies.

SGLT2 and cancer.

Glycolysis plays a central role in tumor metabolism and growth, and this is reflected in a high rate of glucose uptake. It is commonly assumed that the upregulation of the facilitated glucose transporter GLUT1 meets the tumor's demand for sugar. This underlies the success in using 2FDG PET imaging in the clinic to identify and stage many tumors.

Two-Stage Revascularization and Clip Reconstruction of a Giant Ophthalmic Artery Aneurysm: 3-Dimensional Operative Video.

Ophthalmic segment aneurysms (OSAs) are technically challenging lesions with a wide-neck morphology and proximity to the optic nerve. Revascularization and aneurysm trapping are occasionally needed to manage unclippable OSAs. Microsurgical treatment requires anterior clinoidectomy, optic strut drilling, and proximal/distal dural ring dissection for adequate exposure.

Inhibitor binding mode and allosteric regulation of Na-glucose symporters.

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.

Right Pretemporal-Transsylvian Approach for Resection of a Midbrain Cavernous Malformation: 3-Dimensional Operative Video.

Brainstem cavernous malformations (CMs) account for 15% to 18% of all intracranial CMs1 and 13% of all cerebrovascular pathology in the posterior fossa.1,2 This video demonstrates the resection of a pontomesencephalic CM through a pretemporal approach through the oculomotor-tentorial triangle (OTT).3 A 49-yr-old woman presented with an acute onset of left hemiparesis, diplopia, vertigo, partial oculomotor, and facial palsy.

Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2.

The concentration of glucose in plasma is held within narrow limits (4-10 mmol/l), primarily to ensure fuel supply to the brain. Kidneys play a role in glucose homeostasis in the body by ensuring that glucose is not lost in the urine. Three membrane proteins are responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule: sodium-glucose cotransporters SGLT1 and SGLT2, in the apical membrane, and GLUT2, a uniporter in the basolateral membrane.

Transsylvian-Transinsular Approach for an Insular Cavernous Malformation Resection: 3-Dimensional Operative Video.

Surgical resection of insular lesions is challenging due to their proximity to critical neurovascular structures such as the middle cerebral arteries (MCA), Sylvian veins, thalamus, internal capsule (IC), and lenticulostriate arteries. A surgical series using the transsylvian-transinsular approach to treat cerebrovascular pathologies reported ∼5% permanent neurological morbidity.1,2 This case demonstrates the utility of this approach for resecting an insular cavernous malformation (CM).

Clinical and Neurosurgical Management of Cranial Machete Injuries: The Experience of a Tertiary Referral Center in Nicaragua.

Background: The neurosurgical literature rarely describes managing open head injuries caused by machetes, although this is a common head injury in developing countries. We present our experience managing cranial machete injuries in Nicaragua over a 5-year period.

Methods: A retrospective chart review identified patients admitted to a neurosurgery service for cranial machete injury.

Intestinal absorption of glucose in mice as determined by positron emission tomography.

Key Points: The goal was to determine the importance of the sodium-glucose cotransporter SGLT1 and the glucose uniporter GLUT2 in intestinal glucose absorption during oral glucose tolerance tests (OGTTs) in mice. Glucose absorption was determined in mice using positron emission tomography and three non-metabolizable glucose probes: one specific for SGLTs, one specific for GLUTs, and one a substrate for both SGLTs and GLUTs. Absorption was determined in wild-type, Sglt1 and Glut2 mice.

Metastatic Spine Tumor Epidemiology: Comparison of Trends in Surgery Across Two Decades and Three Continents.

Background: Indications for surgery for symptomatic spinal metastases have become better defined in recent years, and suitable outcome measures have been established against a changing backdrop of patient characteristics, tumor behavior, and oncologic treatments. Nonetheless, variations still exist in the local management of patients with spinal metastases. In this study, we aimed to review global trends and habits in the surgical treatment of symptomatic spinal metastases, and to examine how these have changed over the last 25 years.

Positron emission tomography of sodium glucose cotransport activity in high grade astrocytomas.

A novel glucose transporter, the sodium glucose cotransporter 2 (SGLT2), has been demonstrated to contribute to the demand for glucose by pancreatic and prostate tumors, and its functional activity has been imaged using a SGLT specific PET imaging probe, α-methyl-4-[F-18]fluoro-4-deoxy-D-glucopyaranoside (Me-4FDG). In this study, Me-4FDG PET was extended to evaluate patients with high-grade astrocytic tumors. Me-4FDG PET scans were performed in four patients diagnosed with WHO Grade III or IV astrocytomas and control subjects, and compared with 2-deoxy-2-[F-18]fluoro-D-glucose (2-FDG) PET and magnetic resonance imaging (MRI) of the same subjects.

Conformational transitions of the sodium-dependent sugar transporter, vSGLT.

Sodium-dependent transporters couple the flow of Na ions down their electrochemical potential gradient to the uphill transport of various ligands. Many of these transporters share a common core structure composed of a five-helix inverted repeat and deliver their cargo utilizing an alternating-access mechanism. A detailed characterization of inward-facing conformations of the Na-dependent sugar transporter from (vSGLT) has previously been reported, but structural details on additional conformations and on how Na and ligand influence the equilibrium between other states remains unknown.

The First Neurosurgery Boot Camp in Southeast Asia: Evaluating Impact on Knowledge and Regional Collaboration in Yangon, Myanmar.

Background: For the first time in Southeast Asia, a Fundamentals of Neurosurgery Boot Camp was held at the University of Medicine 1 in Yangon, Myanmar, February 24-26, 2017. The aim of this course was to teach and train fundamental skills to neurosurgery residents.

Methods: The Myanmar Neurosurgical Society, Foundation for International Education in Neurosurgery, Society for Neurological Surgeons, The University of Medicine 1 in Yangon, Myanmar, and the Henry Ford Department of Neurosurgery developed a 2-day resident training course.

Active site voltage clamp fluorometry of the sodium glucose cotransporter hSGLT1.

In the human sodium glucose cotransporter (hSGLT1) cycle, the protein undergoes conformational changes where the sugar-binding site alternatively faces the external and internal surfaces. Functional site-directed fluorometry was used to probe the conformational changes at the sugar-binding site. Residues (Y290, T287, H83, and N78) were mutated to cysteines.

Novel and Unexpected Functions of SGLTs.

It has been 30 years since the intestinal sodium glucose cotransporter SGLT1 was cloned, and, in the intervening years, there have been many advances that have influenced physiology and medicine. Among the first was that SGLT1 is the founding member of the human gene family SLC5, containing 11 diverse transporters and a glucose sensor. Equally surprising was that SGLTs are members of a structural family of cotransporters and exchangers in different gene families.

CS-specific modifications of auditory evoked potentials in the behaviorally conditioned rat.

The current report provides a detailed analysis of the changes in the first two components of the auditory evoked potential (AEP) that accompany associative learning. AEPs were recorded from the primary auditory cortex before and after training sessions. Experimental subjects underwent one (n=5) or two (n=7) days of conditioning in which a tone, serving as a conditioned stimulus (CS), was paired with mild foot shock.

Structural and functional significance of water permeation through cotransporters.

Membrane transporters, in addition to their major role as specific carriers for ions and small molecules, can also behave as water channels. However, neither the location of the water pathway in the protein nor their functional importance is known. Here, we map the pathway for water and urea through the intestinal sodium/glucose cotransporter SGLT1.