Regulation of insulin-stimulated glucose transport by chronic glucose exposure in 3T3-L1 adipocytes.
Chronic hyperglycemia causes insulin resistance, termed glucose toxicity. Herein we studied chronic glucose-dependent regulation of the glucose transport system in adipocytes. 3T3-L1 adipocytes were incubated for up to 24 h with low (1 mM) or high (25 mM) glucose, and glucose transport was subsequently analyzed. 100 nM insulin was present throughout the experiments. 24 h incubation with 1 mM glucose caused a 2.3+/-0.4 fold increase in glucose transport activity, compared to the values obtained with 25 mM glucose. This difference was not observed when 24 h incubation was carried out without insulin. Glucose transport activity was not increased at 3 or 6 h incubation with 1 mM glucose, but was increased at 12 h, which closely paralleled increased expression of GLUT1. In addition to increased GLUT1 expression, more efficient translocation of GLUT1 to the plasma membrane was observed when incubated with 1 mM glucose compared to 25 mM glucose. The addition of azaserin or deprivation of glutamine at 25 mM glucose did not increase the glucose transport activity to the level obtained with 1 mM glucose. PD98059 did not affect glucose transport activity when incubated with 1 mM or 25 mM glucose. In conclusion, the present study is the first to show that, in 3T3-L1 adipocytes, chronic exposure to low (1 mM) and high (25 mM) glucose leads to different insulin-stimulated glucose transport activities. These differences result from the difference in the expression and plasma membrane distribution of GLUT1, but not of GLUT4, and the hexosamine biosynthesis pathway or extracellular signal-regulated protein kinase is not involved.
Hosaka
T
T
Third Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Yaga
K
K
Oka
Y
Y
D016475:3T3 Cells / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001377:Azaserine / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage* / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006595:Hexosamines / Q000096:biosynthesis; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D007700:Kinetics; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006595:Hexosamines; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; D001377:Azaserine; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose