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. (C) 1999 American Journal of Hypertension, Ltd.