HEPATIC DENERVATION REDUCES ADRENAL CATECHOLAMINE SECRETION DURING INSULIN-INDUCED HYPOGLYCEMIA

The present study was designed to investigate the functional implication of hepatic afferent nerves in controlling adrenal medullary counterregulatory response to insulin-induced hypoglycemia in anesthetized dogs subjected to an acute surgical denervation of the liver. Aortic glucose concentration decreased similarly in the groups of dogs with hepatic denervation (n = 8) and sham denervation (n = 8) reaching a glucose nadir 30 min after insulin injection (0.15 IU/kg iv) from a control value of 89.46 +/- 3.15 and 88.91 +/- 2.86 mg/dl to 52.92 +/- 3.27 and 48.80 +/- 4.18 mg/dl (P < 0.05), respectively. The catecholamine output from the adrenal glands in the sham group significantly increased (P < 0.05), reaching a maximum level 45 min after insulin injection from a control value for epinephrine of 86.35 +/- 26.65 ng/min and for norepinephrine of 32.14 +/- 11.68 ng/min to 659.03 +/- 269.39 and 181.21 +/- 63.03 ng/min, respectively. By contrast, however, adrenal catecholamine output increased only slightly in the hepatic-denervated group during insulin-induced hypoglycemia, from 148.37 +/- 95.29 and 52.06 +/- 28.05 ng/min to 210.49 +/- 96.09 and 79.61 +/- 26.11 ng/min for epinephrine and norepinephrine, respectively, the difference being statistically nonsignificant compared with the corresponding preinjection control value. The maximum net response of adrenal epinephrine and norepinephrine output observed in dogs with hepatic denervation was significantly attenuated by similar to 90 and 82% of the values obtained from the sham group, respectively. In a separate series of experiments, aortic immunoreactive insulin and glucagon concentrations were measured and found to be similar between hepatic-denervated and sham-denervated groups after insulin-induced hypoglycemia. These results indicate that hepatic afferent nerves are functionally implicated in hepatoadrenal counterregulatory reflex mechanisms during insulin-induced hypoglycemia. The study suggests that the presence of such afferent nerves from the liver is needed for the enhanced release of adrenal catecholamines in response to severe hypoglycemia.