DECREASED GLUT-4 MESSENGER-RNA CONTENT AND INSULIN-SENSITIVE DEOXYGLUCOSE UPTAKE SHOW INSULIN-RESISTANCE IN THE HYPERTENSIVE RAT-HEART

Objectives: Insulin resistance in skeletal muscle and adipose tissue o ften accompanies hypertension; however, it has not been shown that hea rt muscle is similarly affected. The aims of this study were to determ ine whether basal and insulin-stimulated glucose transport and glucose transporter mRNA content are altered in the spontaneously hypertensiv e rat (SHR) heart. Methods: Hearts from 16-18-month-old SHRs were comp ared to their normotensive (WKY) controls. The accumulation of 2-deoxy glucose-6-phosphate (2DG6P), detected using P-31 nuclear magnetic reso nance spectroscopy, was used to assess glucose uptake before and durin g insulin stimulation in the isolated perfused heart. The mRNA levels of both the insulin-sensitive glucose transporter (GLUT-4) and the tra nsporter responsible for basal glucose uptake (GLUT-1) were quantified by Northern blot analysis. Results: The hypertensive rat hearts exhib ited hypertrophy in that the heart/body weight ratio was increased by 59%. In these hearts, the basal rate of glucose uptake was 3-fold grea ter and hexokinase activity was 1.6-fold greater than that of the cont rol rat hearts. On exposure to insulin, accumulation of 2DG6P increase d 5-fold in the control hearts, but only 1.4-fold in the SHR hearts. T hus, in the presence of insulin, the rate of glucose uptake by the hyp ertensive rat heart was significantly (P < 0.05) reduced, being 82% of control. GLUT-4 mRNA content was decreased by 35-49% in the hypertens ive heart (P < 0.01), but there was no significant difference in the G LUT-1 mRNA content. Conclusion: We have demonstrated insulin resistanc e in the hypertrophied heart of the hypertensive rat that may have a m olecular basis in a lower GLUT-4 content.