Corelease of galanin and NE from pancreatic sympathetic nerves during severe hypoglycemia in dogs.
To determine whether norepinephrine (NE) and galanin are coreleased during reflex activation of the sympathetic nervous system by hypoglycemia, we administered insulin to halothane-anesthetized (0.8%) dogs and measured the spillover of NE and galanin-like immunoreactivity (GLIR) into pancreatic venous plasma. Insulin injection produced hypoglycemia [plasma glucose (PG) = 34 +/- 3 mg/dl] but did not activate pancreatic noradrenergic (delta pancreatic NE output = +20 +/- 130 pg/min) or galaninergic nerves (delta GLIR output = +40 +/- 50 fmol/min). To determine whether more severe hypoglycemia would activate these nerves, insulin was administered to dogs infused with somatostatin (SS; 2.5 micrograms/min) to block the counterregulatory increase of glucagon secretion. SS reduced the glucagon response to hypoglycemia by greater than 90%, which allowed PG to decrease to 14 +/- 1 mg/dl. Pancreatic NE output increased by 470 +/- 140 pg/min (P less than 0.005); however, pancreatic GLIR output did not increase significantly (delta = +70 +/- 50 fmol/min). When SS was discontinued, pancreatic NE output increased by 490 +/- 200 pg/min (P less than 0.025), and GLIR output increased by an additional +160 +/- 70 fmol/min (P less than 0.025; total delta from baseline = +230 +/- 90 fmol/min, P less than 0.025), suggesting that SS may restrain pancreatic NE and galanin release. Pancreatic NE and GLIR spillover were also increased during severe hypoglycemia when ganglionic neurotransmission was partially impaired with hexamethonium but not when the neural pathway was interrupted by spinal cord transection. We conclude that NE and galanin are coreleased from pancreatic sympathetic nerves when these nerves are centrally activated during severe hypoglycemia in halothane-anesthetized dogs.
Havel
P J
PJ
Department of Physiological Sciences, School of Veterinary Medicine, University of California, Davis 95616.
Mundinger
T O
TO
Veith
R C
RC
Dunning
B E
BE
Taborsky
G J
GJ
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003714:Denervation; D004285:Dogs; D019004:Galanin; D005730:Ganglionic Blockers / Q000494:pharmacology; D005934:Glucagon / Q000097:blood; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007003:Hypoglycemia / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D010179:Pancreas / Q000294:innervation* / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D012016:Reference Values; D013116:Spinal Cord / Q000502:physiology; D013564:Sympathetic Nervous System / Q000378:metabolism*
D001786:Blood Glucose; D005730:Ganglionic Blockers; D006584:Hexamethonium Compounds; D007328:Insulin; D010455:Peptides; D018738:Hexamethonium; D019004:Galanin; D005934:Glucagon; D009638:Norepinephrine