The effects of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist on insulin resistance in fructose-fed rats

Abstract

The aim of this study was to compare the effects of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor (AT) antagonist on insulin resistance, especially on muscle fiber composition in fructose-induced insulin-resistant and hypertensive rats. Six-week-old male SpragueDawley rats were fed either normal rat chow (control) or a fructose-rich diet (FFR). For the last two weeks of a six-week period of either diet, the rats were treated with gum arabic solution as a vehicle (control or FFR), angiotensin-converting enzyme inhibitor (FFR؉ACE), temocapril (1 mg/kg/ day) or an angiotensin II receptor antagonist (FFR؉AT), CS-866 (0.3 mg/kg/day), by gavage, and then the euglycemic hyperinsulinemic glucose clamp technique was performed to evaluate insulin sensitivity. At the end of the glucose clamp, the soleus muscle was dissected for determination of the muscle fiber composition by ATPase methods. Blood pressure at the glucose clamp in the FFR group was significantly higher than that of the control group, and both temocapril and CS-866 significantly lowered the blood pressure of the FFR group. The average rate of glucose infusion during the glucose clamp, as a measure of insulin sensitivity (M value), was significantly lower in the FFR rats compared to the controls (15.4 ؎ 0.4, 10.9 ؎ 0.6 mg/kg/min, for control and FFR, respectively, P < .01). Both temocapril and CS-866 partially improved the M values compared to FFR (13.2 ؎ 0.7, 12.8 ؎ 0.5 mg/kg/min, for FFR؉ACE, FFR؉AT, respectively, P < .01 compared with FFR, P < .05 compared with control). The composite ratio of type I fibers of the soleus muscle was decreased significantly in the FFR rats compared with the controls (82% ؎ 2%, 75% ؎ 2%, for control and FFR, respectively, P < .01), and both temocapril and CS-866 restored a composite ratio of type I fibers to the same level as that of the controls (81% ؎ 1%, 80% ؎ 1% for FFR؉ACE and FFR؉AT, respectively). The M value was significantly correlated with the composition of type I and type II fibers. These results suggest that the fiber composition of skeletal muscle is correlated to insulin resistance, and that both ACE inhibitors and AT antagonists may modulate the muscle fiber composition in a hypertensive and insulin-resistant animal model, fructose-fed rats, to the same extent. Am J Hypertens 2000;13:290 -297

Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice

“…Natriuretic peptides generally act to antagonise the systemic and local actions of angiotensin II [9]; they are therefore considered as endogenous RAS inhibitors. Growing evidence suggests that inhibition of the RAS exerts a beneficial effect on glycaemic control in experimental models and in clinical studies [44][45][46]. In the present study, we found no significant difference in blood glucose levels between non-Tg and BNP-Tg mice in this type of insulin-deficient model (Table 1).…”

Angiotensin-converting enzyme inhibition reverses diet-induced obesity, insulin resistance and inflammation in C57BL/6J mice

“…19 The actions of ACE inhibition extend beyond blood pressure regulation and improvements in whole-body insulin activity are reported in numerous insulin-resistant rodent models after ACE treatment. 20,21 In addition, ACE inhibitors or angiotensinreceptor blockers reduce both body weight and body fat. 22,23 The ACE inhibitor, captopril (CAP), has been shown to prevent the development of obesity in rodents fed with a high-fat diet, 22,24 although the mechanisms remain unresolved.…”

Dietary obesity-resistance and muscle oxidative enzyme activities of the fast-twitch fibre dominant rat

“…Therefore it has yet to be established whether or not the skeletal muscle fibre composition is a determinant of body fat accumulation. The muscle fibre composition is affected by both environmental and genetic factors, 8 for example, the muscle fibre composition is altered by diet 9,10 and insulin. 11,12 It is hypothesized that the diet causes changes in both the muscle fibre composition and body fat accumulation.…”