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

• Published in: Metabolism, clinical and experimental Vol. 48; no. 8; pp. 1041 - 1046
• Main Authors: Caldiz, Claudia I., Chiappe de Cingolani, Gladys E.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.1999; Elsevier
• Subjects: Adipocytes - drug effects; Adipocytes - metabolism; Animals; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Biological Transport; Diabetes. Impaired glucose tolerance; Enalapril - pharmacology; Enalapril - therapeutic use; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glucose - metabolism; Hypertension - drug therapy; Hypertension - metabolism; Insulin Resistance; Losartan - pharmacology; Losartan - therapeutic use; Medical sciences; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Hypertension; Adipocyte; Animal model; Pancreatic hormone; Rat; Rodentia; Cardiovascular disease; Glucose; Metabolism; Insulin; Uptake; Protein hormone; Target tissue resistance; Vertebrata; Mammalia; Animal
• ISSN: 0026-0495; 1532-8600
• 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 (E max) and the dose of insulin required to elicit 50% of the maximal response (EC 50) were calculated. A diminished E max on lipogenesis without changes in the EC 50 was detected in SHRs. The E max was 0.49 ± 0.09 (SHR) and 1.16 ± 0.14 (WKY) μmol/10 5 cells ( P < .05), and the EC 50 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 μg/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 flow, 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-receptor blocker, it appears that the insulin resistance linked to the hypertension is not related to changes in blood flow.