TY - JOUR
T1 - Redundant parasympathetic and sympathoadrenal mediation of increased glucagon secretion during insulin-induced hypoglycemia in conscious rats
AU - Havel, Peter J
AU - Parry, Susan J.
AU - Stern, Judith S.
AU - Akpan, Jones O.
AU - Gingerich, Ronald L.
AU - Taborsky, Gerald J.
AU - Curry, Donald L.
PY - 1994
Y1 - 1994
N2 - Both the parasympathetic and sympathoadrenal inputs to the pancreas can stimulate glucagon release and are activated during hypoglycemia. However, blockade of only one branch of the autonomic nervous system may not reduce hypoglycemia-induced glucagon secretion, because the unblocked neural input is sufficient to mediate the glucagon response, ie, the neural inputs are redundant. Therefore, to determine if parasympathetic and sympathoadrenal activation redundantly mediate increased glucagon secretion during hypoglycemia, insulin was administered to conscious rats pretreated with a muscarinic antagonist (methylatropine, n = 7), combined α- and β-adrenergic receptor blockade (tolazoline + propranolol, n = 5), or adrenergic blockade + methylatropine (n = 7). Insulin administration produced similar hypoglycemia in control and antagonist-treated rats (25 to 32 mg/dL). In control rats (n = 9), plasma immunoreactive glucagon (IRG) increased from a baseline level of 125 ± 11 to 1,102 ± 102 pg/mL during hypoglycemia (ΔIRG = +977 ± 98 pg/mL, P < .0005). The plasma IRG response was not significantly altered either by methylatropine (ΔIRG = +677 ± 141 pg/mL) or by adrenergic blockade (ΔIRG = +1,374 ± 314 pg/mL). However, the IRG response to hypoglycemia was reduced to 25% of the control value by the combination of adrenergic blockade + methylatropine (ΔIRG = +250 ± 83 pg/mL, P < .01 v control rats). These results suggest that the plasma glucagon response to hypoglycemia in conscious rats is predominately the result of autonomic neural activation, and is redundantly mediated by the parasympathetic and sympathoadrenal divisions of the autonomic nervous system.
AB - Both the parasympathetic and sympathoadrenal inputs to the pancreas can stimulate glucagon release and are activated during hypoglycemia. However, blockade of only one branch of the autonomic nervous system may not reduce hypoglycemia-induced glucagon secretion, because the unblocked neural input is sufficient to mediate the glucagon response, ie, the neural inputs are redundant. Therefore, to determine if parasympathetic and sympathoadrenal activation redundantly mediate increased glucagon secretion during hypoglycemia, insulin was administered to conscious rats pretreated with a muscarinic antagonist (methylatropine, n = 7), combined α- and β-adrenergic receptor blockade (tolazoline + propranolol, n = 5), or adrenergic blockade + methylatropine (n = 7). Insulin administration produced similar hypoglycemia in control and antagonist-treated rats (25 to 32 mg/dL). In control rats (n = 9), plasma immunoreactive glucagon (IRG) increased from a baseline level of 125 ± 11 to 1,102 ± 102 pg/mL during hypoglycemia (ΔIRG = +977 ± 98 pg/mL, P < .0005). The plasma IRG response was not significantly altered either by methylatropine (ΔIRG = +677 ± 141 pg/mL) or by adrenergic blockade (ΔIRG = +1,374 ± 314 pg/mL). However, the IRG response to hypoglycemia was reduced to 25% of the control value by the combination of adrenergic blockade + methylatropine (ΔIRG = +250 ± 83 pg/mL, P < .01 v control rats). These results suggest that the plasma glucagon response to hypoglycemia in conscious rats is predominately the result of autonomic neural activation, and is redundantly mediated by the parasympathetic and sympathoadrenal divisions of the autonomic nervous system.
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U2 - 10.1016/0026-0495(94)90267-4
DO - 10.1016/0026-0495(94)90267-4
M3 - Article
C2 - 8028509
AN - SCOPUS:0028337286
VL - 43
SP - 860
EP - 866
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
SN - 0026-0495
IS - 7
ER -