Role for autonomic nervous system to increase pancreatic glucagon secretion during marked insulin-induced hypoglycemia in dogs.
To determine the role of the autonomic nervous system (ANS) in mediating the glucagon response to marked insulin-induced hypoglycemia in dogs, we measured arterial and pancreatic venous glucagon responses to insulin-induced hypoglycemia during acute, terminal experiments in halothane-anesthetized dogs in which the ANS was intact (control; n = 9), pharmacologically blocked by the nicotinic ganglionic antagonist hexamethonium (n = 6), or surgically ablated by cervical vagotomy and cervical spinal cord section (n = 6). In control dogs, insulin injection caused plasma glucose to fall by 4.4 +/- 0.2 mM to a nadir of 1.7 +/- 0.2 mM. Arterial epinephrine (EPI) levels increased by 13,980 +/- 1860 pM (P less than 0.005), confirming marked activation of the ANS. Pancreatic output of glucagon increased from 0.53 +/- 0.12 to 2.04 +/- 0.38 ng/min during hypoglycemia (change [delta] +1.51 +/- 0.33 ng/min, P less than 0.005). This increased arterial plasma glucagon from 27 +/- 3 to 80 +/- 15 ng/L (delta +52 +/- 14 ng/L, P less than 0.025). Hexamethonium markedly reduced the ANS response to insulin injection (delta EPI +2130 +/- 600 pM, P less than 0.025 vs. control) despite a similar fall of plasma glucose (delta -4.1 +/- 0.2 mM) and a lower nadir (0.6 +/- 0.1 mM). Both the pancreatic glucagon response (delta glucagon output +0.45 +/- 0.2 ng/min) and the arterial immunoreactive glucagon response (delta +5 +/- 4 ng/L) were substantially reduced by hexamethonium (P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiological Sciences, School of Veterinary Medicine, University of California-Davis 95616.
P J
PJ
Havel
R C
RC
Veith
B E
BE
Dunning
G J
GJ
Taborsky
D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology / Q000503:physiopathology*; D001786:Blood Glucose / Q000378:metabolism*; D004285:Dogs; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D006400:Hematocrit; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D009638:Norepinephrine / Q000097:blood; D010179:Pancreas / Q000098:blood supply; D012039:Regional Blood Flow / Q000187:drug effects; D013116:Spinal Cord / Q000502:physiology; D014628:Vagotomy
D001786:Blood Glucose; D006584:Hexamethonium Compounds; D007328:Insulin; D018738:Hexamethonium; D005934:Glucagon; D009638:Norepinephrine; D004837:Epinephrine