Resistance to exercise-induced increase in glucose uptake during hyperinsulinemia in insulin-resistant skeletal muscle of patients with type 1 diabetes

Insulin and exercise have been shown to activate glucose transport at least in part via different signaling pathways. However, it is unknown whether i nsulin resistance is associated with a defect in the ability of an acute bo ut of exercise to enhance muscle glucose uptake in vivo. We compared the ab ilities of insulin and isometric exercise to stimulate muscle blood flow an d glucose uptake in 12 men with type 1 diabetes (age 24 a 1 years, BMI 23.0 +/- 0.4 kg/m(2)) and in 11 age- and weight-matched nondiabetic men (age 25 +/- 1 years, BMI 22.3 +/- 0.6 kg/m(2)) 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 (r ange 45-150). Rates of muscle blood flow, oxygen consumption, and glucose u ptake were quantitated simultaneously in both legs using [O-15]water, [O-15 ]oxygen, [F-18]-2-fluoro-2-deoxy-D-glucose, and positron emission tomograph y. Resting rates of oxygen consumption were similar during hyperinsulinemia between the groups (2.4 +/- 0.3 vs. 2.0 +/- 0.5 ml.kg(-l) muscle.min(-1); normal subjects versus patients with type 1 diabetes, NS), and exercise inc reased oxygen consumption similarly in both groups (25.3 +/- 4.3 vs. 20.1 /- 3.0 ml.kg(-1) muscle min,respectively, NS). Rates of insulin-stimulated muscle blood flow and the increments in muscle blood flow induced by exerci se 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 patien ts with type 1 diabetes exhibited resistance to both insulin stimulation of glucose uptake (34 a 6 vs. 76 +/- 9 mu mol.kg(-1) muscle.min(-1), P < 0.00 1) and also to the exercise-induced increment in glucose uptake (82 <plus/m inus> 15 vs. 162 +/- 29 mu mol.kg(-1) muscle.min(-1), P < 0.05). We conclud e that the ability of exercise to increase insulin-stimulated glucose uptak e in vivo is blunted in patients with insulin-resistant type 1 diabetes com pared with normal subjects. This could be caused by either separate or comm on defects in exercise- and insulin-stimulated pathways.