Activation of raphe pallidus neurons increases insulin through medullary thyrotropin-releasing hormone (TRH)-vagal pathways.
BACKGROUND
Pancreatic insulin secretion is regulated by the vagus nerve. Medullary thyrotropin-releasing hormone (TRH) containing projections from the raphe pallidus (Rpa) neurons innervate vagal preganglionic motor neurons in the dorsal vagal complex (DVC) and are involved in vagal regulation of gastric functions.


OBJECTIVE
To investigate whether chemical stimulation of Rpa neurons influences circulating insulin levels through brain medullary TRH-vagal pathways.


METHODS
In fasted, pentobarbital-anesthetized rats, kainic acid (10 ng/50 nL) was microinjected into the Rpa, and serum insulin levels were measured. Gastric acid secretion was monitored as a control of vagally mediated visceral response.


RESULTS
Chemical stimulation of Rpa neuronal cell bodies significantly increased serum insulin levels. Values before and at 30, 60, and 90 minutes after the microinjection of kainic acid were 0.34 +/- 0.02, 0.54 +/- 0.06, 0.60 +/- 0.06, and 0.99 +/- 0.13 ng/mL, respectively. In the same rats, gastric acid secretion was stimulated (basal, 2.3 +/- 0.6, versus 26.1 +/- 8.6 micromol/15 min at 30 minutes). Microinjections outside of the Rpa had no effect. The Rpa stimulation-induced increase in serum insulin could be mimicked by DVC microinjection of TRH analog, completely prevented by bilateral cervical vagotomy, and significantly reduced by bilateral microinjection of TRH antibody into the DVC.


CONCLUSIONS
Chemical activation of Rpa neurons increases pancreatic insulin release through medullary TRH and vagal-mediated pathways.
Yang
Hong
H
Center for Ulcer Research & Education, Veterans Affairs Greater Los Angeles Healthcare System, UCLA Department of Medicine, and Brain Research Institute, Los Angeles, California 90073, USA. hoyang@ucla.edu
Taché
Yvette
Y
Ohning
Gordon
G
Go
Vay Liang W
VL
D000818:Animals; D005744:Gastric Acid / Q000378:metabolism; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology; D007328:Insulin / Q000097:blood*; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology*; D008845:Microinjections; D009431:Neural Conduction; D009474:Neurons / Q000502:physiology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology* / Q000601:surgery
D007074:Immunoglobulin G; D007328:Insulin; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D007608:Kainic Acid; D011761:Pyrrolidonecarboxylic Acid