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 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.
Caldiz
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CI
Center of Cardiovascular Research, School of Medicine, National University of La Plata, Argentina.
de Cingolani
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GE
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001692:Biological Transport; D004656:Enalapril / Q000494:pharmacology* / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D007333:Insulin Resistance; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents; D004656:Enalapril; D005947:Glucose; D019808:Losartan