Selective amylin inhibition of the glucagon response to arginine is extrinsic to the pancreas

Citation
Ra. Silvestre et al., Selective amylin inhibition of the glucagon response to arginine is extrinsic to the pancreas, AM J P-ENDO, 280(3), 2001, pp. E443-E449
Citations number
36
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
ISSN journal
01931849 → ACNP
Volume
280
Issue
3
Year of publication
2001
Pages
E443 - E449
Database
ISI
SICI code
0193-1849(200103)280:3<E443:SAIOTG>2.0.ZU;2-I
Abstract
Amylin, a peptide hormone from pancreatic beta -cells, is reported to inhib it insulin secretion in vitro and in vivo and to inhibit nutrient-stimulate d glucagon secretion in vivo. However, it has been reported not to affect a rginine-stimulated glucagon secretion in vitro. To resolve if the latter re sulted from inactive peptide (a problem in the early literature), those exp eriments were repeated here with well-characterized peptide and found to be valid. In isolated perfused rat pancreas preparations, coperfusion with 1 nM amylin had no effect on arginine-, carbachol-, or vasoactive intestinal peptide-stimulated glucagon secretion. Amylin also had no effect on glucago n output stimulated by decreasing glucose concentration from 11 to 3.2 mM o r on glucagon suppression caused by increasing glucose from 3.2 to 7 mM. Am ylin at 100 nM had no effect in isolated islets in which glucagon secretion was stimulated by exposure to 10 mM arginine, even though glucagon secreti on in the same preparation was inhibited by somatostatin. In anesthetized r ats, amylin coinfusion had no effect on glucagon secretion stimulated by in sulin-induced hypoglycemia. To reconcile reports of glucagon inhibition wit h the absence of effect in the experiments just described, anesthetized rat s coinfused with rat amylin or with saline were exposed sequentially to int ravenous L-arginine (during a euglycemic clamp) and then to hypoglycemia. A mylin inhibited arginine- induced, but not hypoglycemia-induced, glucagon s ecretion in the same animal. In conclusion, we newly identify a selective g lucagonostatic effect of amylin that appears to be extrinsic to the isolate d pancreas and may be centrally mediated.