Pancreatic sympathetic nerves contribute to increased glucagon secretion during severe hypoglycemia in dogs

To determine if pancreatic sympathetic nerves can contribute to increased glucagon secretion during hypoglycemia, plasma glucagon and pancreatic glucagon secretion in situ were measured before and during insulin-induced hypoglycemia in three groups of halothane-anesthetized dogs. All dogs were bilaterally vagotomized to eliminate the input from pancreatic parasympathetic nerves. One group of dogs received only vagotomy (VAGX). A second group was vagotomized and adrenalectomized (VAGX + ADX). A third group received vagotomy, adrenalectomy, plus surgical denervation of the pancreas (VAGX + ADX + NERVX) to prevent activation of pancreatic sympathetic nerves. In dogs with VAGX only, hypoglycemia increased plasma epinephrine (Epi), pancreatic norepinephrine (NE) output (+320 ± 140 pg/min, P < 0.05), arterial plasma glucagon (+28 ± 12 pg/ml, P < 0.01), and pancreatic glucagon output (+ 1,470 ± 370 pg/min, P < 0.01). The addition of ADX eliminated the increase of Epi but did not increase pancreatic NE output (+370 ± 190 pg/min P < 0.025), arterial plasma glucagon (+20 ± 5 pg/ml, P < 0.01), or pancreatic glucagon output (+ 810 ± 200 pg/min, P < 0.01). In contrast, the addition of pancreatic denervation eliminated the increase of pancreatic NE output (-20 ± 40 pg/min, P < 0.05 vs. VAGX), the arterial glucagon (+ 1 ± 2 pg/ml, P < 0.01 vs. VAGX), and pancreatic glucagon output responses (+210 ± 280 pg/min, P < 0.025 vs. VAGX) to hypoglycemia. Thus activation of pancreatic sympathetic nerves can contribute to the increased glucagon secretion during severe insulin-induced hypoglycemia in dogs.