Alteration of muscle fiber composition linking to insulin resistance and hypertension in fructose-fed rats

The aim of this study was to examine the role of muscle fiber composition in insulin resistance and the effect of a calcium channel antagonist on insulin sensitivity in fructose-induced insulin resistant and hypertensive rats. Six-week-old male Sprague-Dawley rats were fed either normal rat chow (control) or fructose-rich diet (FFR). For the last 2 weeks of a 6-week period of either diet, the rats were treated, by gavage, with gum arabic solution (control or FFR) or a dihydropyridine calcium channel antagonist, benidipine hydrochloride (3 mg/kg/day: FFR + Ca), then the euglycemic hyperinsulinemic glucose clamp technique was performed to evaluate insulin sensitivity. Blood pressure was measured weekly for 6 weeks. At the end of the glucose clamp, the soleus muscle was dissected out for determination of muscle fiber composition by ATPase methods. Blood pressure was elevated at 2 weeks after the start of fructose-rich chow feeding and persisted thereafter throughout the study. Blood pressure at the glucose clamp in the FFR was significantly higher than that in the control group (142 ± 2 v 155 ± 2 mm Hg, P< .01) and the calcium antagonist significantly lowered blood pressure of FFR (136 ± 6 mm Hg for FFR + Ca, P< .05). The average rate of glucose infusion during glucose clamp, as a measure of insulin sensitivity (M value), was significantly lower in the FFR than in the control (15.4 ± 0.4 v 10.9 ± 0.6 mg/kg/min, P< .01). The calcium channel antagonist partially improved the M value compared to that of FFR (13.4 ± 0.7 mg/kg/min in FFR + Ca, P< .01 compared to FFR, P< .05 compared to control). The composite ratio of type I fiber in soleus muscle was significantly decreased in FFR compared to control (81.7 ± 1.5% v 75.0 ± 1.7%, P< .01), and the composite ratio of type I fiber in rats treated with the calcium channel antagonist (FFR + Ca) recovered to the control level (79.9 ± 1.1%, P< .05 compared to FFR). The M value was significantly correlated with the compositions of type I and type II fibers (for type I fibers, r = 0.80, P< .01; for type II fibers, r = −0.81, P< .01). These results suggest that fiber composition of skeletal muscle links insulin resistance and that a calcium channel antagonist may modulate muscle fiber composition in hypertensive animal model, fructose-fed rats.