Ci. Caldiz et Gec. De Cingolani, Insulin resistance in adipocytes from spontaneously hypertensive rats: Effect of long-term treatment with enalapril and losartan, METABOLISM, 48(8), 1999, pp. 1041-1046
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.