Abstract

Insulin and exercise have been shown to activate glucose transport at least in part via different signaling pathways. However, it is unknown whether insulin resistance is associated with a defect in the ability of an acute bout of exercise to enhance muscle glucose uptake in vivo. We compared the abilities of insulin and isometric exercise to stimulate muscle blood flow and glucose uptake in 12 men with type 1 diabetes (age 24 ± 1 years, BMI 23.0 ± 0.4 kg/m²) and in 11 age- and weight-matched nondiabetic men (age 25 ± 1 years, BMI 22.3 ± 0.6 kg/m²) during euglycemic hyperinsulinemia (1 mU · kg⁻¹ · min⁻¹ insulin infusion for 150 min). One-legged exercise was performed at an intensity of 10% of maximal isometric force for 105 min (range 45–150). Rates of muscle blood flow, oxygen consumption, and glucose uptake were quantitated simultaneously in both legs using [¹⁵O]water, [¹⁵O]oxygen, [¹⁸F]-2-fluoro-2-deoxy-d-glucose, and positron emission tomography. Resting rates of oxygen consumption were similar during hyperinsulinemia between the groups (2.4 ± 0.3 vs. 2.0 ± 0.5 ml · kg⁻¹ muscle · min⁻¹; normal subjects versus patients with type 1 diabetes, NS), and exercise increased oxygen consumption similarly in both groups (25.3 ± 4.3 vs. 20.1 ± 3.0 ml · kg⁻¹ muscle · min⁻¹, respectively, NS). Rates of insulin-stimulated muscle blood flow and the increments in muscle blood flow induced by exercise were also similar in normal subjects (129 ± 14 ml · kg⁻¹ · min⁻¹) and in patients with type 1 diabetes (115 ± 12 ml · kg⁻¹ · min⁻¹). The patients with type 1 diabetes exhibited resistance to both insulin stimulation of glucose uptake (34 ± 6 vs. 76 ± 9 μmol · kg⁻¹ muscle · min⁻¹, P < 0.001) and also to the exercise-induced increment in glucose uptake (82 ± 15 vs. 162 ± 29 μmol · kg⁻¹ muscle · min⁻¹, P < 0.05). We conclude that the ability of exercise to increase insulin-stimulated glucose uptake in vivo is blunted in patients with insulin-resistant type 1 diabetes compared with normal subjects. This could be caused by either separate or common defects in exercise- and insulin-stimulated pathways.