It now seems that adipose hexose transfer is subject to at least two forms of regulation - the well-documented, insulin-induced carrier recruitment from cytosol to plasma membrane and a recruitment-independent mechanism. Here we show that both rat adipose and erythrocyte sugar transport may share a common susceptibility to regulation by this 'recruitment'-independent mechanism. The kinetics of sugar transport in normal rat adipose and erythrocytes are symmetric. Following rat hypophysectomy, however, both adipose and RBC sugar transport become asymmetric - exit rates being greater than those for entry. Under these conditions, insulin accelerates adipose sugar uptake but not exit. The striking parallels between adipose and RBC hexose transfer responses to hypophysectomy have enabled us to exploit the RBC as a model system for the study of this type of transport regulation. The result has been the discovery of 'active principles' in both rat serum and RBC cytosol from hypophysectomized rats that control the expression of red cell sugar transport symmetry, the number of RBC hexose transport proteins and the average molecular weight of the transporter. Our goal is to exploit this endocrinological approach to determine: 1. The origin of increased RBC hexose transfer protein numbers. 2. The molecular basis of RBC transport symmetry expression. 3. The susceptibility of adipose hexose transfer to these transport modulating factors. 4. The effects of these factors on insulin-induced adipose carrier recruitment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK036081-02
Application #
3234402
Study Section
Metabolism Study Section (MET)
Project Start
1985-09-25
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655
Ojelabi, Ogooluwa A; Lloyd, Kenneth P; De Zutter, Julie K et al. (2018) Red wine and green tea flavonoids are cis-allosteric activators and competitive inhibitors of glucose transporter 1 (GLUT1)-mediated sugar uptake. J Biol Chem 293:19823-19834
Lloyd, Kenneth P; Ojelabi, Ogooluwa A; Simon, Andrew H et al. (2018) Kinetic Basis of Cis- and Trans-Allostery in GLUT1-Mediated Sugar Transport. J Membr Biol 251:131-152
Lloyd, Kenneth P; Ojelabi, Ogooluwa A; De Zutter, Julie K et al. (2017) Reconciling contradictory findings: Glucose transporter 1 (GLUT1) functions as an oligomer of allosteric, alternating access transporters. J Biol Chem 292:21035-21046
Ojelabi, Ogooluwa A; Lloyd, Kenneth P; Simon, Andrew H et al. (2016) WZB117 (2-Fluoro-6-(m-hydroxybenzoyloxy) Phenyl m-Hydroxybenzoate) Inhibits GLUT1-mediated Sugar Transport by Binding Reversibly at the Exofacial Sugar Binding Site. J Biol Chem 291:26762-26772
Sage, Jay M; Carruthers, Anthony (2014) Human erythrocytes transport dehydroascorbic acid and sugars using the same transporter complex. Am J Physiol Cell Physiol 306:C910-7
De Zutter, Julie K; Levine, Kara B; Deng, Di et al. (2013) Sequence determinants of GLUT1 oligomerization: analysis by homology-scanning mutagenesis. J Biol Chem 288:20734-44
Vollers, Sabrina S; Carruthers, Anthony (2012) Sequence determinants of GLUT1-mediated accelerated-exchange transport: analysis by homology-scanning mutagenesis. J Biol Chem 287:42533-44
Cura, Anthony J; Carruthers, Anthony (2012) Role of monosaccharide transport proteins in carbohydrate assimilation, distribution, metabolism, and homeostasis. Compr Physiol 2:863-914
Cura, Anthony J; Carruthers, Anthony (2012) AMP kinase regulation of sugar transport in brain capillary endothelial cells during acute metabolic stress. Am J Physiol Cell Physiol 303:C806-14
Mangia, Silvia; DiNuzzo, Mauro; Giove, Federico et al. (2011) Response to 'comment on recent modeling studies of astrocyte-neuron metabolic interactions': much ado about nothing. J Cereb Blood Flow Metab 31:1346-53

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