Paternostro G, Clarke K, Heath J, Seymour A M, Radda G K
Department of Biochemistry, University of Oxford, UK.
Cardiovasc Res. 1995 Aug;30(2):205-11.
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.
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.
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 was no significant difference in the GLUT-1 mRNA content.
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.
骨骼肌和脂肪组织中的胰岛素抵抗常与高血压相伴；然而，尚无研究表明心肌也受到类似影响。本研究旨在确定自发性高血压大鼠（SHR）心脏中基础状态及胰岛素刺激下的葡萄糖转运和葡萄糖转运蛋白mRNA含量是否发生改变。
将16 - 18月龄SHR的心脏与其正常血压（WKY）对照进行比较。使用31P核磁共振波谱法检测2 - 脱氧葡萄糖 - 6 - 磷酸（2DG6P）的积累，以评估离体灌注心脏在胰岛素刺激前后的葡萄糖摄取情况。通过Northern印迹分析对胰岛素敏感的葡萄糖转运蛋白（GLUT - 4）和负责基础葡萄糖摄取的转运蛋白（GLUT - 1）的mRNA水平进行定量。
高血压大鼠心脏表现出肥大，心脏/体重比增加了59%。在这些心脏中，基础葡萄糖摄取率比对照大鼠心脏高3倍，己糖激酶活性高1.6倍。暴露于胰岛素时，对照心脏中2DG6P的积累增加了5倍，而SHR心脏中仅增加了1.4倍。因此，在有胰岛素存在的情况下，高血压大鼠心脏的葡萄糖摄取率显著降低（P < 0.05），仅为对照的82%。GLUT - 4 mRNA含量降低，GLUT - 1 mRNA含量无显著差异。
我们已证实在高血压大鼠肥大心脏中存在胰岛素抵抗，其分子基础可能是GLUT - 4含量降低。
