Decreased leg glucose uptake during exercise contributes to the hyperglycaemic effect of octreotide

During prolonged infusion of somatostatin, there is an increase in arterial glucose concentration, and this increase persists even during prolonged exercise. The aim of the study was to measure glucose uptake in the leg muscles during infusion of the somatostatin analogue octreotide before and during leg exercise.

Eight healthy male subjects were investigated twice in the fasting state: during 3 h infusion of octreotide [30 ng (kg min)(-1)] or sodium chloride with exercise at 50% of maximal VO(2) in the last hour. Glucose uptake and oxygen uptake in the leg were measured using Fick's principle by blood sampling from an artery and a femoral vein. Blood flow in the leg was measured using the indicator (indocyanine green) dilution technique.

After an initial decrease during rest, octreotide infusion resulted in a significant increase in arterial glucose concentrations compared to control conditions during exercise (mean +/- SEM: 7.6 +/- 0.6 versus 5.6 +/- 0.1 mmol l(-1), P<0.01). During rest, octreotide did not change the leg glucose uptake (59 +/- 10 versus 55 +/- 11 micromol min(-1)). In contrast, leg glucose uptake was significantly lower during exercise compared to control conditions (208 +/- 79 versus 423 +/- 87 micromol min(-1), P<0.05). During exercise, leg oxygen uptake was not different in the two experiments (20.4 +/- 1.3 versus 19.5 +/- 1.1 micromol min(-1)).

In conclusion, infusion of octreotide reduced leg glucose uptake during exercise, despite the same leg oxygen consumption and blood flow compared to control conditions. The hyperglycaemic effect of octreotide can partly be explained by the reduction in leg glucose uptake. Furthermore, the results suggest that a certain level of circulating insulin is necessary to obtain sufficient stimulation of glucose uptake in the exercising muscles.