Intracellular targeting of the insulin-regulatable glucose transporter (GLUT4) is isoform specific and independent of cell type.

Abstract

. Insulin stimulates glucose transport in adipocytes via the rapid redistribution of the GLUT! and GLUT4 glucose transporters from intracellular membrane compartments to the cell surface. Insulin sensitivity is dependent on the proper intracellular trafficking of the glucose transporters in the basal state. The bulk of insulin-sensitive transport in adipocytes appears to be due to the translocation of GLUT4, which is more efficiently sequestered inside the cell and is present in much greater abundance than GLUTI.The cell type and isoform specificity of GLUT4 intracellular targeting were investigated by examining the subcellular distribution of GLUTI and GLUT4 in cell types that are refractory to the effect of insulin on glucose transport. Rat GLUT4 was expressed in 3T3-LI fibroblasts and HepG2 hepatoma cells by DNAmediated transfection . Transfected 3T3-Ll fibroblasts over-expressing human GLUTI exhibited increased glucose transport, and laser confocal immunofluorescent imaging of GLUTI in these cells indicated that the protein was concentrated in the plasma membrane. In contrast, 3T3-Ll fibroblasts expressing GLUT4 exhibited no increase in transport activity, and confocal imaging demonstrated that this protein was targeted almost exclusively to cytoplasmic compartments . 3T3-Ll fibroblasts expressing GLUT4 were unresponsive to r.UCOSE, an essential nutrient for many mammalian cells, is transported across the plasma membrane via facilitative carrier proteins . Five glucose transporter isoforms have been described thus far (for reviews, see Gould and Bell, 1990;Mueckler, 1990). These are named GLUTI through GLUT5 in order of their identification by means of cDNA cloning. The five transporter isoforms are distinguished by their discrete tissue distributions, kinetic properties, and regulation . In most cell types, such as endothelial cells, hepatocytes, and parenchymal cells of the brain, glucose transport is probably not rate limiting for glu-

Distinct signals in the GLUT4 glucose transporter for internalization and for targeting to an insulin-responsive compartment.

“…The expression of GLUT1 and GLUT4 in several cell types has demonstrated that, in spite of 65% identity in amino acid sequence, each isoform possesses distinct information conferring subcellular targeting (18,23,28,35). Experimental strategies based on the construction of chimeric transporter proteins have led to identification of several structural domains implicated as critical to the intracellular sequestration of GLUT4 (11,27,29,30,43).…”

Hyperglycaemia-induced subcellular redistribution of GLUT1 glucose transporters in cultured human term placental trophoblast cells

“…This binding is saturable and competitively inhibited by peptide 480±492 [19]. The antiserum cross-reacts with the HepG2 glucose transporter [20] as well as with GLUT1 in Caco-2 cells [21].…”

Astragalus polysaccharides alleviates glucose toxicity and restores glucose homeostasis in diabetic states via activation of AMPK

“…The glucose transporter 4 (GLUT4) is the key signaling molecule that coordinates glucose conversion and metabolism with glucose transport. In response to a signal, GLUT4 is translocated from the cytoplasm to the plasma membrane, where it facilitates the entry of glucose into the cell and produces a marked cellular response [9,10] . When pathogenic factors disturb the translocation of GLUT4, the cells cannot utilize glucose, which accumulates and causes the harmful condition known as "glucose toxicity" [11] .…”