Insulin is necessary for glucose uptake in the periphery. It induces the translocation of GLUT4, a specific insulin-sensitive glucose transporter, to the plasma membrane of fat cells and muscle cells. Chronic elevation of insulin has been known to cause downregulation of this transporter, leading to reduced insulin-mediated glucose uptake. The fact that glucagon-like peptide-1 (GLP-1) an incretin hormone, modulated insulin signalling in the 3T3-L1 adipocytes (Endocrinology 135:2070-2075, 1994) prompted us to investigate the effects of GLP-1 on the GLUT4 transporter in these cells. It appeared that GLP-1 could reverse the downregulation induced by high concentration of insulin on GLUT4 mRNA levels. GLP-1 also caused an increase in the levels of GLUT1 mRNA and protein, GLUt1 being widely distributed among all tissues. In conjunction with these findings, we also showed that the downregulation of GLUT4 mRNA induced by insulin in cells incubated with 22mM glucose could be prevented by reducing the glucose concentration in the medium. The C/EBP family of transcription factors is coexpressed with adipocyte genes (e.g. GLUT4) during the differentiation of 3T3-L1 adipocytes. We looked at the relationship between gadd 153 (which encodes a C/EBP-related protein that lacks a functional DNA-binding domain), C/EBP alpha and GLUT4, and found an association between the mRNA levels for C/EBP and GLUT4 in a variety of culture conditions. It appeared, however, that the levels of gadd 153 mRNA differed from that of C/EBP alpha depending on the glucose levels in the culture medium.
NIH ExPorter
NIH ExPorter