HIGH-FAT DIET REDUCES GLUCOSE-TRANSPORTER RESPONSES TO BOTH INSULIN AND EXERCISE

High-fat diet (HFD) induces skeletal muscle insulin resistance. To inv estigate associated changes in the plasma membrane glucose transporter , male Sprague-Dawley rats were fed either chow [high-carbohydrate die t (HCD)] or HFD for 3 wk. Plasma membrane vesicles were prepared from hindlimb muscle of control, insulin-stimulated (Ins), and acutely exer cised (Ex) rats. Maximal vesicle glucose transport activity (V-max) in creased threefold with Ins and Ex treatment compared with controls in HCD rats; in HFD rats, increases were less than twofold. Transporter n umbers (measured by cytochalasin B binding, CB) approximately doubled with Ins and Ex in both diet groups. Intrinsic activity (carrier turno ver, V-max/CB) increased significantly with stimulation in HCD but not HFD rats. Therefore, vesicles from HFD rats showed resistance to both exercise and insulin stimulation of muscle glucose transport. Transpo rter number increased normally, but intrinsic activity in HFD rats did not respond. Two conclusions are discussed: 1) translocation and acti vation are distinct, separable steps in transporter stimulation and 2) HFD produces effects that resemble the insulin resistance of starvati on.