Selective hypoglycemia in the liver induces adrenomedullary counterregulatory response

The present study was designed to investigate adrenal medullary responses to a selective regional hypoglycemia in the liver of dogs with hepatic cross-perfusion. The liver of recipient dogs (Re) was perfused with vena caval and aortic blood of donor dogs (Dn) through the portal vein and hepatic artery, respectively. Total hepatic venous blood of Re was returned to Dn through the left jugular vein. Upon the cross-perfusion, glucose (Glc, 5%) was infused at an average rate of 3.5 +/- 0.2 mg . kg(-1) . min(-1) (n = 12) in Re to compensate the loss of hepatic Glc delivery into the systemic circulation. Insulin (5.0 IU/kg iv) was administered to Dn followed by infusion with an average rate of 0.95 +/- 0.17 IU . kg(-1) min(-1) (n = 6), and this served as the hepatic hypoglycemic group. Saline was similarly administered to Dn, which served as the normoglycemic control group. In the hepatic hypoglycemic group, aortic and vena caval Glc levels in Dn, which represent Glc concentrations entering the liver of Re, decreased from 129.9 +/- 7.1 and 122.5 +/- 7.8 to 44.6 +/- 6.1 and 38.0 +/- 5.9 mg/dl (P < 0.05) 45 min after insulin administration, respectively. During this regional hepatic hypoglycemia in Re, the systemic glycemia being kept within a normal range, adrenal epinephrine and norepinephrine output increased from 245.5 +/- 55.8 and 39.1 +/- 9.9 to 618.9 +/- 180.4 and 134.3 +/- 52.7 ng/min (P < 0.05), respectively. By contrast, aortic Glc and insulin levels in Dn of the normoglycemic control group remained unchanged, as did adrenal epinephrine and norepinephrine output in Re. The results indicate that the regional hepatic hypoglycemia can significantly increase adrenal catecholamine secretion even during systemic (central) normoglycemia. The study suggests that the hepatoadrenal Glc counterregulatory reflex may be functionally implicated in insulin-induced hypoglycemia.