ramipril and Hyperinsulinism

This study was designed to investigate the effect of short-term ACE inhibitor treatment on insulin sensitivity and to examine possible underlying metabolic and haemodynamic effects in obese insulin-resistant subjects.. A randomised, double-blind placebo-controlled trial was performed in 18 obese insulin-resistant men (age, 53 +/- 2 years; BMI, 32.6 +/- 0.8 kg/m(2); homeostasis model assessment of insulin resistance, 5.6 +/- 0.5; systolic blood pressure [SBP], 140.8 +/- 3.2; diastolic blood pressure [DBP], 88.8 +/- 1.6 mmHg), who were free of any medication. The aim was to examine the effects of 2 weeks of ACE inhibitor treatment (ramipril, 5 mg/day) on insulin sensitivity, forearm blood flow, substrate fluxes across the forearm, whole-body substrate oxidation and intramuscular triacylglycerol (IMTG) content.. Ramipril treatment decreased ACE activity compared with placebo (-22.0 +/- 1.7 vs 0.2 +/- 1.1 U/l, respectively, p < 0.001), resulting in a significantly reduced blood pressure (SBP, -10.8 +/- 2.1 vs -2.7 +/- 2.0 mmHg, respectively, p = 0.01; DBP, -10.1 +/- 1.3 vs -4.2 +/- 2.1 mmHg, respectively, p = 0.03). Ramipril treatment had no effect on whole-body insulin-mediated glucose disposal (before: 17.9 +/- 2.0, after: 19.1 +/- 2.4 micromol kg body weight(-1) min(-1), p = 0.44), insulin-mediated glucose uptake across the forearm (before: 1.82 +/- 0.39, after: 1.92 +/- 0.29 micromol 100 ml forearm tissue(-1) min(-1), p = 0.81) and IMTG content (before: 45.4 +/- 18.8, after: 48.8 +/- 27.5 micromol/mg dry muscle, p = 0.92). Furthermore, the increase in carbohydrate oxidation (p < 0.001) and forearm blood flow (p < 0.01), and the decrease in fat oxidation (p < 0.001) during insulin stimulation were not significantly different between treatments.. Short-term ramipril treatment adequately reduced ACE activity and blood pressure, but had no significant effects on insulin sensitivity, forearm blood flow, substrate fluxes across the forearm, whole-body substrate oxidation and IMTG content in obese insulin-resistant subjects.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Blood Pressure; Double-Blind Method; Fatty Acids, Nonesterified; Glucose Clamp Technique; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Middle Aged; Placebos; Ramipril

The contribution of nondegraded bradykinin to the metabolic effects of the angiotensin-converting enzyme (ACE)-kininase II inhibitor ramipril was evaluated in rats rendered hypertensive, hyperinsulinemic, and hypertriglyceridemic by a fructose-enriched diet. The response of blood pressure, insulin, and triglyceride levels to concomitant administration of ramipril and the bradykinin antagonist HOE 140 was studied. Rats that received ramipril, HOE 140, or not treated at all served as controls. Treatment with ramipril reduced levels of both insulin (from 6.6 +/- 2.0 to 3.6 +/- 1.7 ng/ml; p < 0.05) and triglycerides (from 292 +/- 88 to 164 +/- 35 mg/dl; p < 0.001) as well as blood pressure (from 144 +/- 6 to 116 +/- 6 mm Hg; p < 0.001). In contrast, treatment with HOE 140 did not alter any of these parameters. The combined treatment, however, blunted the beneficial metabolic effects of ramipril on insulin (7.8 +/- 4.4 ng/ml before and 7.7 +/- 2.9 ng/ml after treatment) and triglycerides (290 +/- 135 mg/dl before and 285 +/- 152 mg/dl after treatment), whereas the hypotensive effect of ramipril was preserved (151 +/- 8 mm Hg before and 122 +/- 6 mm Hg after treatment (p < 0.001). The data suggest that whereas the hypotensive effect is mostly angiotensin-II dependent, the advantageous metabolic affect of ramipril is highly dependent on the accumulation of bradykinin.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Bradykinin; Fructose; Hyperinsulinism; Hyperlipidemias; Hypertension; Insulin; Male; Ramipril; Rats; Rats, Sprague-Dawley; Triglycerides