GLUT4-containing vesicles cycle between the plasma membrane and intracellular compartments. Insulin promotes GLUT4 exocytosis by regulating GLUT4 vesicle arrival at the cell periphery and its subsequent tethering, docking, and fusion with the plasma membrane. The molecular machinery involved in GLUT4 vesicle tethering is unknown. We show here that Myo1c, an actin-based motor protein that associ...

We used an improved cryosectioning technique in combination with quantitative immunoelectron microscopy to study GLUT4 compartments in isolated rat white adipose cells. We provide clear evidence that in unstimulated cells most of the GLUT4 localizes intracellularly to tubulovesicular structures clustered near small stacks of Golgi and endosomes, or scattered throughout the cytoplasm. This local...

Background: Oleuropein, the main constituent of olive fruit and leaves, has been reported to protect against insulin resistance and diabetes. While many experimental investigations have examined the mechanisms by which oleuropein improves insulin resistance and diabetes, much of these investigations have been carried out in either muscle cell lines or in vivo models two scenarios with many draw...

Glucose transporter type 4 (GLUT4) is insulin responsive and is expressed in striated muscle and adipose tissue. To investigate the impact of a partial deficiency in the level of GLUT4 on in vivo insulin action, we examined glucose disposal and hepatic glucose production (HGP) during hyperinsulinemic clamp studies in 4-5-mo-old conscious mice with one disrupted GLUT4 allele [GLUT4 (+/-)], compa...

GLUT4 shows decreased levels in failing human adult hearts. We speculated that GLUT4 expression in cardiac muscle may be fine-tuned by microRNAs. Forced expression of miR-133 decreased GLUT4 expression and reduced insulin-mediated glucose uptake in cardiomyocytes. A computational miRNA target prediction algorithm showed that KLF15 is one of the targets of miR-133. It was confirmed that over-exp...

Insulin stimulates GLUT4 (glucose transporter 4) translocation in adipocytes and muscles. An emerging picture is that Rab10 could bridge the gap between the insulin signalling cascade and GLUT4 translocation in adipocytes. In the present study, two potential effectors of Rab10, GDI (guanine-nucleotide-dissociation inhibitor)-1 and GDI-2, are characterized in respect to their roles in insulin-st...

The synthetic thiazolidinedione ligands of peroxisome proliferator-activated receptor-gamma (PPARgamma) improve insulin sensitivity in type II diabetes and induce GLUT4 mRNA expression in fat and muscle. However, the molecular mechanisms involved are still unclear. We studied the regulatory effects of PPARgamma and its ligands on GLUT4 gene expression in primary rat adipocytes and CHO-K1 cells ...

Insulin-mediated glucose uptake is highly sensitive to the levels of the facilitative glucose transporter protein, GLUT4. Repression of GLUT4 expression is correlated with insulin resistance in adipose tissue. We have shown that differentiation-dependent GLUT4 transcription was under control of class II histone deacetylases (HDACs). We hypothesized that HDACs may regulate gene expression in adi...

Insulin-stimulated delivery of glucose transporter-4 (GLUT4) to the plasma membrane (PM) is the hallmark of glucose metabolism. In this study we examined insulin's effects on GLUT4 organization in PM of adipose cells by direct microscopic observation of single monomers tagged with photoswitchable fluorescent protein. In the basal state, after exocytotic delivery only a fraction of GLUT4 is disp...

Exercise induces an increase in GLUT4 in skeletal muscle with a proportional increase in glucose transport capacity. This adaptation results in enhanced glycogen accumulation, i.e., "supercompensation," in response to carbohydrate feeding after glycogen-depleting exercise. The increase in GLUT4 reverses within 40 h after exercise in carbohydrate-fed rats. The purpose of this study was to determ...