Effects of comorbid type II diabetes mellitus and heart failure on rat hindlimb and respiratory muscle blood flow during treadmill exercise

Abstract

In rats with type 2 diabetes mellitus (T2DM) compared to non-diabetic healthy controls, muscle blood flow (Q̇m) to primarily glycolytic hindlimb muscles and the diaphragm muscle are elevated during submaximal treadmill running consequent to lower skeletal muscle mass, a finding that held even when muscle mass was normalized to body mass. In rats with heart failure with reduced ejection fraction (HF-rEF) compared to healthy controls, hindlimb Q̇m was lower, while diaphragm Q̇m is elevated during submaximal treadmill running. Importantly, T2DM is the most common co-morbidity present in HF-rEF patients, but the effect of concurrent T2DM and HF-rEF on limb and respiratory Q̇m during exercise is unknown. We hypothesized that during treadmill running (20 m·min-1; 10% incline) hindlimb and diaphragm Q̇m would be higher in T2DM Goto-Kakizaki rats with HF-rEF (i.e., HF-rEF+T2DM) compared to non-diabetic Wistar rats with HF-rEF. Ejection fractions were not different between groups (HF-rEF: 30±5; HF-rEF+T2DM: 28±8 %; P=0.617), whereas blood glucose was higher in HF-rEF+T2DM (209±150 mg/dL) compared with HF-rEF rats (113±28 mg/dL; P=0.040). Hindlimb muscle mass normalized to body mass was lower in rats with HF-rEF+T2DM (36.3±1.6 mg/g) compared to non-diabetic HF-rEF counterparts (40.3±2.7 mg/g; P<0.001). During exercise Q̇m was elevated in rats with HF-rEF+T2DM compared with non-diabetic counterparts to the hindlimb (HF-rEF: 100±28; HF-rEF+T2DM: 139±23 mL·min-1·100g-1; P<0.001) and diaphragm (HF-rEF: 177±66; HF-rEF+T2DM: 215±93 mL·min-1·100g-1; P=0.035). These data suggest that the pathophysiological consequences of T2DM on hindlimb and diaphragm Q̇m during treadmill running in the GK rat persist even in the presence of HF-rEF.