Insulin resistance in adipocytes from spontaneously hypertensive rats: Effect of long-term treatment with enalapril and losartan

Insulin responsiveness was studied in isolated adipocytes from the normoten sive Wistar Kyoto (WKY) rat and the spontaneously hypertensive rat (SHR), T he effect of insulin (0.1 to 5 nmol/L) on glucose uptake (glucose transport and lipogenesis) was measured, and the maximal effect of insulin (E-max) a nd the dose of insulin required to elicit 50% of the maximal response (EC50 ) were calculated. A diminished E-max on lipogenesis without changes in the EC50 was detected in SHRs, The E-max was 0.49 +/- 0.09 (SHR) and 1.16 +/- 0.14 (WKY) mu mol/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 o btained when measuring insulin-stimulated glucose transport, A 30-day long- term treatment with enalapril (20 mg/kg/d) normalized insulin responsivenes s in adipocytes from SHRs. The effect of enalapril was suppressed when SHRs were pretreated with enalapril and 150 mu g/kg/d of the bradykinin (BK) B- 2-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 fl ow, and the effect of insulin in the SHR was improved by pretreatment with an angiotensin-converting enzyme (ACE) inhibitor but not with the AT(1)-rec eptor blocker, it appears that the insulin resistance linked to the hyperte nsion is not related to changes in blood flow. Copyright (C) 1999 by W.B. S aunders Company.