Insulin resistance and GLUT-4 glucose transporter in adipocytes from hypertensive rats

Abstract

To investigate the mechanisms that cause insulin resistance in hypertension, experiments were performed to study the effect of insulin on glucose transport, GLUT-4 translocation from intracellular to plasma membranes and GLUT-4 phosphorylation in isolated adipocytes from normotensive Wistar (W) and spontaneously hypertensive rats (SHR). Glucose transport was measured in adipocytes incubated with 3- O- d[Methyl- 3H] glucose with and without insulin (0.1 to 5 nmol/L). GLUT-4 protein was determined by Western blot immunoanalysis with GLUT-4 antibody. Phosphorylation of GLUT-4 was measured by immunoprecipitation with GLUT-4 antibody followed by immunoanalysis with phosphoserine or phosphothreonine antibodies. Compared with adipocytes from W, insulin-stimulated glucose transport was lower in the SHR ( P < .05). GLUT-4 protein expression was similar in adipocytes from W and SHR. Insulin increased GLUT-4 translocation from intracellular to plasma membranes in both groups. This effect was lower in the SHR ( P < .05). The effect of insulin on GLUT-4 serine phosphorylation showed no changes in plasma membranes from W and decreased in the SHR ( P < .05). In intracellular membranes, insulin increased specific GLUT-4 serine phosphorylation in both groups ( P < .05), but the increase was lower in the SHR ( P < .05). The results suggest that a deficient GLUT-4 translocation to plasma membranes in response to insulin shown in adipocytes from SHR, which was accompanied by a decrease in GLUT-4 phosphorylation at serine site, could be one of the causes of insulin resistance in hypertension.