INSULIN-INDUCED GLUT4 RECRUITMENT IN THE FATTY ZUCKER RAT-HEART IS NOT ASSOCIATED WITH CHANGES IN GLUT4 CONTENT IN THE INTRACELLULAR MEMBRANE

Impaired cardiac glucose metabolism and glucose transport have been sh own in the insulin resistant fatty Zucker rat. The aim of the present study was to examine the translocation of the insulin-sensitive glucos e transporter (Glut4) in the heart of the fatty Zucker rat under in vi vo conditions. Insulin was injected into both lean (FA/?) and fatty (f a/fa) Zucker rats via the tail vein. The time course of cardiac Glut4 translocation was studied by determining the subcellular distribution of Glut4 using a newly developed ELISA quantitation method. Insulin (1 0 U/kg) caused a 30% and 37% increase in plasma membrane Glut4, conten t at 20 min after injection in lean and fatty rats respectively. The p lasma membrane Glut4 contents in the basal and insulin-stimulated stat es were significantly lower in the fatty rat when compared to the lean control. The dose effect of insulin (2.5-10 U/kg) on Glut4, mobilizat ion to the plasma membrane was similar in both phenotypes. The time co urse of Glut4 mobilization to the plasma membrane (5-30 min), which wa s similar in both lean and fatty Zucker rats, showed that maximal tran slocation was reached at 5 min post insulin injection and persisted th roughout the remaining 25 min. However, in fatty Zucker rats, Glut4 co ntent in the intracellular membrane remained unchanged at all insulin doses and all time points studied. Collectively, these results show th at Glut4 recruitment to the plasma membrane is responsive to insulin i n the fatty Zucker rat heart and that the maximal response was similar to that in lean Zucker rats. However, the recruitment of Glut4 to the plasma membrane was not associated with changes in the intracellular membrane Glut4, content.