Insulin resistance and GLUT-4 glucose transporter in adipocytes from hypertensive rats.
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-(3)H] 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.
Chiappe De Cingolani
Gladys E
GE
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
Caldiz
Claudia I
CI
D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002469:Cell Separation; D004591:Electrophoresis, Polyacrylamide Gel; D051275:Glucose Transporter Type 4; D006973:Hypertension / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D010766:Phosphorylation; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism
D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat