Caldiz C I, de Cingolani G E
Center of Cardiovascular Research, School of Medicine, National University of La Plata, Argentina.
Metabolism. 1999 Aug;48(8):1041-6. doi: 10.1016/s0026-0495(99)90203-2.
Insulin responsiveness was studied in isolated adipocytes from the normotensive Wistar Kyoto (WKY) rat and the spontaneously hypertensive rat (SHR). The effect of insulin (0.1 to 5 nmol/L) on glucose uptake (glucose transport and lipogenesis) was measured, and the maximal effect of insulin (Emax) and the dose of insulin required to elicit 50% of the maximal response (EC50) were calculated. A diminished Emax on lipogenesis without changes in the EC50 was detected in SHRs. The Emax was 0.49 +/- 0.09 (SHR) and 1.16 +/- 0.14 (WKY) micromol/10(5) cells (P < .05), and the EC50 was 0.13 +/- 0.03 and 0.11 +/- 0.02 nmol/L for WKY and SHR, respectively. Similar results were obtained when measuring insulin-stimulated glucose transport. A 30-day long-term treatment with enalapril (20 mg/kg/d) normalized insulin responsiveness in adipocytes from SHRs. The effect of enalapril was suppressed when SHRs were pretreated with enalapril and 150 microg/kg/d of the bradykinin (BK) B2-receptor blocker Hoe 140. Pretreatment with losartan (40 mg/kg/d) did not improve insulin action in the SHR. Since these results were obtained with isolated cells in which glucose availability was not a function of blood flow, and the effect of insulin in the SHR was improved by pretreatment with an angiotensin-converting enzyme (ACE) inhibitor but not with the AT1-receptor blocker, it appears that the insulin resistance linked to the hypertension is not related to changes in blood flow.
在正常血压的Wistar Kyoto（WKY）大鼠和自发性高血压大鼠（SHR）的分离脂肪细胞中研究了胰岛素反应性。测量了胰岛素（0.1至5 nmol/L）对葡萄糖摄取（葡萄糖转运和脂肪生成）的影响，并计算了胰岛素的最大效应（Emax）和引发最大反应50%所需的胰岛素剂量（EC50）。在SHR中检测到脂肪生成的Emax降低，而EC50没有变化。Emax分别为0.49±0.09（SHR）和1.16±0.14（WKY）μmol/10(5)个细胞（P<0.05），WKY和SHR的EC50分别为0.13±0.03和0.11±0.02 nmol/L。在测量胰岛素刺激的葡萄糖转运时也获得了类似的结果。用依那普利（20 mg/kg/d）进行30天的长期治疗可使SHR脂肪细胞中的胰岛素反应性恢复正常。当用依那普利和150 μg/kg/d的缓激肽（BK）B2受体阻滞剂Hoe 140预处理SHR时，依那普利的作用受到抑制。用氯沙坦（40 mg/kg/d）预处理并不能改善SHR中的胰岛素作用。由于这些结果是在分离细胞中获得的，其中葡萄糖可用性不是血流的函数，并且SHR中胰岛素的作用通过用血管紧张素转换酶（ACE）抑制剂预处理而不是用AT1受体阻滞剂预处理得到改善，因此似乎与高血压相关的胰岛素抵抗与血流变化无关。
