The abnormality of glucose transporter in the erythrocyte membrane of Chinese type 2 diabetic patients.
Type 2 diabetes mellitus is characterized by impaired glucose uptake. With a photometric method of recording the erythrocyte suspension absorption during the course of glucose transport across the membranes, we observed that the initial rate of glucose zero-trans entry was decreased significantly in 30 Chinese type 2 diabetic patients as compared to 25 healthy controls. The rate of glucose infinite-cis efflux exhibited no difference between the patients and controls. The measurement of temperature dependence of glucose transport showed that the activation energy for glucose entry was increased in diabetic patients. The inhibitory constant of glucose entry by cytochalasin B (CB) in patients was similar to that of the controls. However, we found that the inhibitory constant was increased significantly in the patient erythrocytes after phloretin treatment. After the erythrocytes were made into stripped white ghosts, the fluorescence quenching experiment was performed. Glucose, CB and phloretin can quench the fluorescence of tryptophan residues in the glucose transporter 1, GLUT1. The abnormality of fluorescence quenching in the erythrocyte membranes of patients was observed. The transfer tendency of tryptophan residues from the hydrophilic environment to the hydrophobic environment was decreased in patient ghosts as binding with glucose, and the opposite tendency appeared as CB and phloretin instead of glucose. We conclude that the decreased in glucose entry in the erythrocyte membranes of diabetic patients was due to the GLUT1 change in structure - mostly the outer domain of the glucose transporter.
Hu
X J
XJ
Department of Physiology and Biophysics, Liren Laboratory, Fudan University, Shanghai, China.
Peng
F
F
Zhou
H Q
HQ
Zhang
Z H
ZH
Cheng
W Y
WY
Feng
H F
HF
D044466:Asian People; D002681:China; D003571:Cytochalasin B / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004734:Energy Metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D006801:Humans; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D010693:Phloretin / Q000378:metabolism
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D003571:Cytochalasin B; D005947:Glucose; D010693:Phloretin