Sympathetic drive to liver and nonhepatic splanchnic tissue during prolonged exercise is increased in diabetes

This study was conducted to assess whether nonhepatic splanchnic (NHS) and hepatic tissues contribute to the increase in circulating norepinephrine during prolonged exercise, and to determine whether such a response is exaggerated during exercise in the poorly controlled diabetic when the arterial norepinephrine response is excessive. Chronically catheterized (carotid artery, portal vein, and hepatic vein) and instrumented (Doppler flow probes on hepatic artery and portal vein) normal (n = 6) and alloxan-diabetic (n = 5) dogs were studied during rest (30 minutes) and moderate treadmill exercise (150 minutes). Basal plasma glucose of diabetic dogs was threefold that of control dogs. Since epinephrine is not released by splanchnic tissues, NHS and hepatic epinephrine fractional extraction (FX) can be accurately measured. Because epinephrine FX = norepinephrine FX, norepinephrine spillover can be calculated. NHS and hepatic epinephrine FX remained stable during rest and exercise in both control and diabetic dogs. Although basal NHS norepinephrine spillover was not different between the two groups, basal hepatic norepinephrine spillover was lower in the controls (1.1 +/- 0.3 ng/kg . min) compared with the diabetics (3.6 +/- 1.1 ng/kg . min). Although NHS norepinephrine spillover increased with exercise in the normal dog (3.1 +/- 0.6 ng/kg . min at t = 150 minutes), there was no increase in hepatic norepinephrine spillover (1.1 +/- 0.3 ng/kg . min at t = 150 minutes). In contrast, NHS (8.8 +/- 1.6 ng/kg . min at t = 150 minutes) and hepatic (6.9 +/- 1.8 ng/kg . min at t = 150 minutes) norepinephrine spillover were both markedly increased in the diabetic dog to rates approximately threefold and sixfold higher than in the normal dog. These data show that an increase in NHS but not hepatic norepinephrine spillover is a component of the normal response to prolonged exercise. The exaggerated increase in arterial norepinephrine during exercise in the diabetic state is due, in part, to both increased sympathetic drive to the gut and liver. This increase in sympathetic drive to the splanchnic bed may contribute to the deleterious effects of exercise in poorly controlled diabetes.