© 1995 by European Society of Cardiology
Copyright © 1995, European Society of Cardiology
Decreased GLUT-4 mRNA content and insulin-sensitive deoxyglucose uptake show insulin resistance in the hypertensive rat heart
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
* Corresponding author. Tel. (1865)275255; Fax (1865)275259.
Objectives: Insulin resistance in skeletal muscle and adipose tissue often accompanies hypertension; however, it has not been shown that heart muscle is similarly affected. The aims of this study were to determine whether basal and insulin-stimulated glucose transport and glucose transporter mRNA content are altered in the spontaneously hypertensive rat (SHR) heart. Methods: Hearts from 16–18-month-old SHRs were compared to their normotensive (WKY) controls. The accumulation of 2-deoxyglucose-6-phosphate (2DG6P), detected using 31P nuclear magnetic resonance spectroscopy, was used to assess glucose uptake before and during insulin stimulation in the isolated perfused heart. The mRNA levels of both the insulin-sensitive glucose transporter (GLUT-4) and the transporter responsible for basal glucose uptake (GLUT-1) were quantified by Northern blot analysis. Results: The hypertensive rat hearts exhibited hypertrophy in that the heart/body weight ratio was increased by 59%. In these hearts, the basal rate of glucose uptake was 3-fold greater and hexokinase activity was 1.6-fold greater than that of the control rat hearts. On exposure to insulin, accumulation of 2DG6P increased 5-fold in the control hearts, but only 1.4-fold in the SHR hearts. Thus, in the presence of insulin, the rate of glucose uptake by the hypertensive rat heart was significantly (P < 0.05) reduced, being 82% of control. GLUT-4 mRNA content was decreased by 35–49% in the hypertensive heart (P < 0.01), but there was no significant difference in the GLUT-1 mRNA content. Conclusion: We have demonstrated insulin resistance in the hypertrophied heart of the hypertensive rat that may have a molecular basis in a lower GLUT-4 content.
KEYWORDS Insulin resistance; Hypertension; Hypertrophy; GLUT-1; GLUT-4; Glucose transport; Nuclear magnetic resonance spectroscopy
1 Present address: Cyclotron Unit, MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, DuCane Road, London W12 ONN, UK.
2 Present address: Department of Cardiothoracic Surgery, National Heart and Lung Institute at Harefield Hospital, Harefield, Middlesex, UB9 6JH, UK.
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