Human erythrocyte glucose sugar transport was examined in resealed red cell ghosts under equilibrium exchange conditions ([sugar](intracellular) = [sugar](extracellular), where brackets indicate concentration). Exchange 3-O-methylglucose (3MG) import and export are monophasic in the absence of cytoplasmic ATP but are biphasic when ATP is present. Biphasic exchange is observed as the rapid filling of a large compartment (66% cell volume) followed by the slow filling of the remaining cytoplasmic space. Biphasic exchange at 20 mM 3MG eliminates the possibility that the rapid exchange phase represents ATP-dependent 3MG binding to the glucose transport protein (GLUT1; cellular [GLUT1] of =20 microM). Immunofluorescence-activated cell sorting analysis shows that biphasic exchange does not result from heterogeneity in cell size or GLUT1 content. Nucleoside transporter-mediated uridine exchange proceeds as rapidly as 3MG exchange but is monoexponential regardless of cytoplasmic [ATP]. This eliminates cellular heterogeneity or an ATP-dependent, nonspecific intracellular diffusion barrier as causes of biphasic exchange. Red cell ghost 3MG and uridine equilibrium volumes (130 fl) are unaffected by ATP. GLUT1 intrinsic activity is unchanged during rapid and slow phases of 3MG exchange. Two models for biphasic sugar transport are presented in which 3MG must overcome a sugar-specific, physical (diffusional), or chemical (isomerization) barrier to equilibrate with cell water. Partial transport inhibition with the use of cytochalasin B or maltose depresses both rapid and slow phases of transport, thereby eliminating the physical barrier hypothesis. We propose that biphasic 3MG transport results from ATP-dependent, differential transport of 3MG anomers in which V(max)/apparent K(m) for beta-3MG exchange transport is 19-fold greater than V(max)/apparent K(m) for alpha-3MG transport.
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http://dx.doi.org/10.1152/ajpcell.00335.2006 | DOI Listing |
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Indian Institute of Technology, Gandhinagar, India.
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Alzheimers Dement
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Department of Neurology, Mayo Clinic, Rochester, MN, USA.
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Columbia University, New York, NY, USA.
Background: Genome-wide association studies (GWAS) have identified genetic loci that robustly associate with Alzheimer's Disease (AD), many of which are preferentially or exclusively expressed in innate immune cells. Among the identified AD risk genes is CD33: a transmembrane, sialic acid-binding protein expressed on the surface of myeloid cells including microglia, the innate immune cells of the CNS. The function of microglia is highly responsive to and regulated by metabolic changes, which allows them to rapidly change phenotype and maintain brain health.
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January 2025
Health Services Management Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran.
The impact of blood glucose-lowering medications on weight has always been a topic of interest in the treatment of diabetic patients. This study investigates the effect of empagliflozin on weight in patients with prediabetes and type 2 diabetes. This quasi-experimental study was performed on patients with prediabetes or type 2 diabetes with an HbA1c level up to 1% higher than the treatment target, and not using other blood glucose-lowering medications.
View Article and Find Full Text PDFNat Commun
January 2025
Center of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.
Glucose deprivation, a hallmark of the tumor microenvironment, compels tumor cells to seek alternative energy sources for survival and growth. Here, we show that glucose deprivation upregulates the expression of mitochondrial-cytochrome c oxidase II (MT-CO2), a subunit essential for the respiratory chain complex IV, in facilitating glutaminolysis and sustaining tumor cell survival. Mechanistically, glucose deprivation activates Ras signaling to enhance MT-CO2 transcription and inhibits IGF2BP3, an RNA-binding protein, to stabilize MT-CO2 mRNA.
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