INHIBITION OF ANGIOTENSIN TYPE-1 RECEPTOR PREVENTS DECLINE OF GLUCOSE-TRANSPORTER (GLUT4) IN DIABETIC RAT-HEART

There is some evidence that inhibition of angiotensin-converting enzym e (ACE) activity can improve the uptake and conversion of glucose by h eart and skeletal muscle in diabetes. To study the underlying mechanis ms, we treated streptozotocin-induced diabetic rats with the angiotens in type 1 receptor (AT(1)) antagonist ICI D8731 and the ACE inhibitor fosinopril for 4 months and determined the expression of the myocardia l glucose transporter proteins. In diabetic rats, the expression of th e insulin-regulated glucose transporter (GLUT4) was strongly diminishe d as shown by Western and Northern blots. ICI D8731 prevented the decr ease of GLUT4 protein in diabetes but had no influence on the amount o f mRNA encoding for GLUT1 and GLUT4. GLUT1 protein was hardly detected in the rat heart and was affected neither by diabetes nor by treatmen t with the AT(1) antagonist. Additionally, ICI D8731 influenced the tr anslocation of GLUT4 from the intracellular pool to the plasma membran e, because treatment increased the amount of GLUT4 protein in the plas ma membranes as well as in intracellular membrane fractions compared w ith membranes of untreated diabetic control rats. In contrast, inhibit ion of ACE by fosinopril influenced neither the expression nor the tra nslocation of the glucose transporter proteins. These observations ind icate that angiotensin II has a distinct influence on the posttranscri ptional regulation of the GLUT4 transporter protein, presumably indire ctly as a consequence of hemodynamic effects and structural alteration s of the vessel wall.