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This study was designed to examine the effects of an angiotensin II receptor antagonist on insulin sensitivity in an insulin-resistant hypertensive rat model (fructose-fed rats; FFR). Male Sprague-Dawley rats were fed a fructose-rich diet or standard chow for 4 weeks and then treated with either 1 mg/kg/day of TCV-116 (angiotensin II receptor antagonist) or vehicle for a further 2 weeks. Steady-state plasma glucose (SSPG) was measured while the animals were conscious. Insulin (2.5 mU/kg/min) and glucose (8 mg/kg/min) were simultaneously infused to determine insulin sensitivity in each group. The mean arterial pressure (MAP) was higher in the FFR (133 +/- 5 mmHg) than in the control group (120 +/- 3), and TCV-116 (110 +/- 4) decreased MAP significantly. SSPG was also higher in the FFR group (207 +/- 6 mg/dl) than in the control (137 +/- 10, p < 0.01), and TCV-116 (171 +/- 7) significantly reduced SSPG. The FFR group also had higher steady-state plasma insulin (SSPI) levels than the control (107 +/- 10 microU/ml for FFR and 63 +/- 12 for control, p < 0.05), and TCV-116 attenuated the increase in SSPI (73 +/- 11, p < 0.05). Thus, the angiotensin II receptor antagonist improved insulin resistance, as assessed by determining SSPG in FFR, suggesting that angiotensin II antagonism may play an important role in improving of insulin resistance in FFR.
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