AJP - Endocrinology and Metabolism, Vol 254, Issue 4 E513-E517, Copyright © 1988 by American Physiological Society
Peptide YY antagonizes beta-adrenergic-stimulated release of insulin in dogs
G. H. Greeley Jr, F. Lluis, G. Gomez, J. Ishizuka, B. Holland and J. C. Thompson
Department of Surgery, University of Texas Medical Branch, Galveston 77550.
Peptide YY (PYY) and neuropeptide Y (NPY) are peptides of 36 amino acids
that share structural homologies with pancreatic polypeptide (PP). PP is
predominantly found in the endocrine pancreas. PPY is primarily found in
mucosal endocrine cells of the distal ileum, colon, and rectum, whereas NPY
is found in both the peripheral and central nervous systems. Previous
studies indicate that these peptides can interact with the autonomic
nervous system. The objective of the present experiments was to study the
effect of PYY on neurally stimulated insulin release [i.e., in response to
2-deoxy-D-glucose (2-DG), a nonmetabolizable glucose analogue] in conscious
dogs. Intravenous administration of PYY (100, 200, and 400 pmol.kg-1.h-1)
reduced 2-DG-stimulated insulin release in a dose-dependent manner (P less
than 0.05) without affecting plasma glucose levels. Administration of NPY
(800 pmol.kg-1.h-1), but not PP (400 pmol.kg-1.h-1), reduced
2-DG-stimulated release of insulin (P less than 0.05). The inhibitory
action of PYY on 2-DG-stimulated insulin release persisted in the presence
of atropine or phentolamine treatment; however, hexamethonium alone or
phentolamine plus propranolol treatment blocked the inhibitory action of
PYY. Release of insulin stimulated by the beta-agonist isoproterenol was
also inhibited by PYY (P less than 0.05). These results indicate that PYY
can inhibit autonomic neurotransmission by a mechanism that may involve
ganglionic or postganglionic inhibition of beta-adrenergic stimulation. Our
findings suggest a role for PYY and NPY in the autonomic regulation of
insulin release.
