Analysis of the Glucose Transporter Compliment of Metabolically Important Tissues from the Milan Hypertensive Rat

Hypertension is frequently associated with peripheral insulin resistance. An expanding body of evidence has described aberrant expression of glucose transporters in the insulin resistance associated with diabetes mellitus. Therefore, we have investigated the relative levels of expression and subcellular distribution of four members of the facilitative glucose transporter family in metabolically important tissues from the hypertensive Milan rat. Skeletal muscle is the major site of peripheral glucose disposal; skeletal muscle membranes isolated from hypertensive animals exhibited a profoundly reduced level of GLUT4 protein compared to normotensive control animals This reduction was confined to the intracellular pool which exhibited a 50% lower level of GLUT4. In contrast, adipocytes, the other major site of peripheral glucose disposal, exhibited no change in the levels of expression of either GLUT1 or GLUT4 transporter isoforms. Hepatocytes from hypertensive animals exhibit similar levels of GLUT2 protein to the normotensive controls. Patterns of expression of GLUT1, GLUT3 and GLUT4 as determined by immunoblot analysis were profoundly altered in certain brain regions in the hypertensive state. Given the importance of the GLUT4 isoform in mediating the insulin-stimulated disposal of glucose into peripheral tissues, the observation that muscle exhibits profoundly decreased levels of this transporter has important implications for the insulin-resistance associated with hypertension in these animals.