Regulation of Insulin-Stimulated Glucose Transport by Chronic Glucose Exposure in 3T3-L1 Adipocytes

摘要

References(29) Cited-By(7) 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 24h with low (1mM) or high (25mM) glucose, and glucose transport was subsequently analyzed. 100nM insulin was present throughout the experiments. 24h incubation with 1mM glucose caused a 2.3±0.4 fold increase in glucose transport activity, compared to the values obtained with 25mM glucose. This difference was not observed when 24h incubation was carried out without insulin. Glucose transport activity was not increased at 3 or 6h incubation with 1mM glucose, but was increased at 12h, 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 1mM glucose compared to 25mM glucose. The addition of azaserin or deprivation of glutamine at 25mM glucose did not increase the glucose transport activity to the level obtained with 1mM glucose. PD98059 did not affect glucose transport activity when incubated with 1mM or 25mM glucose. In conclusion, the present study is the first to show that, in 3T3-L1 adipocytes, chronic exposure to low (1mM) and high (25mM) 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.