Adrenergic mechanisms in the metabolic adaptation to fasting and feeding: Effects of phlorizin on diet-induced changes in sympathoadrenal activity in the rat

Recent studies from our laboratory have demonstrated that fasting and feeding exert important effects on the activity of the sympathetic nervous system in the rat: fasting suppresses, and overfeeding sucrose stimulates the sympathetic nervous system. Furthermore, changes in sympathetic activity with changes in caloric intake have been clearly dissociated from the adrenal medullary response to hypoglycemia that develops in fasting pregnant rats, a model of fasting hypoglycemia in which suppression of the sympathetic nervous system occurs despite profound stimulation of the adrenal medulla. To examine the relationships between food intake, hypoglycemia, and the functional state of the sympathetic nervous system and adrenal medulla, studies were conducted in rats treated with the renal glucosuric agent phlorizin. In the ad lib fed state rats given phlorizin increased chow intake 79%. Despite this increase in chow intake, cardiac norepinephrine turnover was not affected by phlorizin administration and urinary epinephrine excretion and adrenal epinephrine content were unaltered. In phlorizin-treated rats fasted for 3 days, overt hypoglycemia developed (plasma glucose 49.3 ± 2.7 mg/dl as compared with 116 ± 3.2 in phlorizin-treated fed rats) and a significant increase in the urinary excretion of epinephrine and norepinephrine occurred. Cardiac norepinephrine turnover was not increased despite profound adrenal medullary stimulation (54% decrease in adrenal epinephrine content). In phlorizin-treated, adrenal demedullated animals fasting was not associated with a rise in either norepinephrine or epinephrine excretion. The effect of sucrose feeding on cardiac norepinephrine turnover was similar in phlorizin-treated and control animals. These experiments provide additional evidence that the activity of the sympathetic nervous system and the adrenal medulla may be dissociated by fasting hypoglycemia and that the urinary excretion of norepinephrine cannot be assumed to reflect exclusively or predominantly the activity of the sympathetic nervous system. The results also imply that increased chow intake per se, and the associated increase in nutrient processing in the gut, does not increase the activity of the sympathetic nervous system. The results are discussed in terms of the signal that couples changes in diet with changes in sympathetic activity.