Neural regulation of glucagon-like peptide-1 secretion in pigs.
Glucagon-like peptide (GLP)-1 is secreted rapidly from the intestine postprandially. We therefore investigated its possible neural regulation. With the use of isolated perfused porcine ileum, GLP-1 secretion was measured in response to electrical stimulation of the mixed, perivascular nerve supply and infusions of neuroactive agents alone and in combination with different blocking agents. Electrical nerve stimulation inhibited GLP-1 secretion, an effect abolished by phentolamine. Norepinephrine inhibited secretion, and phentolamine abolished this effect. GLP-1 secretion was stimulated by isoproterenol (abolished by propranolol). Acetylcholine stimulated GLP-1 secretion, and atropine blocked this effect. Dimethylphenylpiperazine stimulated GLP-1 secretion. In chloralose-anesthetized pigs, however, electrical stimulation of the vagal trunks at the level of the diaphragm had no effect on GLP-1 or GLP-2 and weak effects on glucose-dependent insulinotropic peptide and somatostatin secretion, although this elicited a marked atropine-resistant release of the neuropeptide vasoactive intestinal polypeptide to the portal circulation. Thus GLP-1 secretion is inhibited by the sympathetic nerves to the gut and may be stimulated by intrinsic cholinergic nerves, whereas the extrinsic vagal supply has no effect.
Dept. of Medical Physiology, University of Copenhagen, the Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
Lene
L
Hansen
Sarah
S
Lampert
Hitoshi
H
Mineo
Jens J
JJ
Holst
D000109:Acetylcholine / Q000502:physiology; D018663:Adrenergic Agents / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000187:drug effects / Q000502:physiology*; D005768:Gastrointestinal Hormones / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D007082:Ileum / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000502:physiology; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism*; D013153:Splanchnic Nerves / Q000502:physiology; D013552:Swine; D014630:Vagus Nerve / Q000502:physiology
D018663:Adrenergic Agents; D005768:Gastrointestinal Hormones; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D011498:Protein Precursors; D001285:Atropine; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D007545:Isoproterenol; D000109:Acetylcholine; D009638:Norepinephrine; D010646:Phentolamine