1. Exchange of metabolic substrates was studied across the leg at rest and during a bicycle exercise demanding 50% of the maximal oxygen uptake in seven patients with juvenile diabetes and six control subjects. The leg blood flow and the femoral arterial and venous substrate concentrations were measured in the fasting state and, in the diabetic subjects, 24 h after the last administration of insulin.

2. At rest a close correlation was seen in the control subjects between the leg glucose uptake and the arterial insulin concentration. The diabetic subjects, including three patients in whom it could be shown that the insulin concentrations were extremely low, had a resting glucose uptake in the same order of magnitude as the control subjects. The glucose uptake was inversely related to the arterial concentrations of non-esterified fatty acids in both groups.

3. During exercise the glucose uptake increased in both patients and control subjects, but the increase was not related to arterial concentrations of insulin or non-esterified fatty acids.

4. The release of lactate, pyruvate, alanine and glycerol from the leg was not different in diabetic and control subjects neither at rest nor during exercise.

5. The ketonaemia was increased in the diabetic subjects, but the uptake of total ketone bodies was not different in the two groups. No increase in the uptake of total ketone bodies in control and diabetic subjects was found during exercise. The leg uptake of acetoacetate was a function of the substrate load and tended to be higher in diabetic subjects during exercise, when no net uptake of β-hydroxybutyrate was found.

6. The above results suggest that the glucose uptake in human skeletal muscle at rest depends on the concentration of insulin and possibly also of non-esterified fatty acids in arterial blood. In contrast the glucose uptake during exercise is not related to the concentration of insulin or non-esterified fatty acids, which may explain why no differences in this aspect are seen between the leg metabolism of diabetic and normal subjects.

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