Ag. Nieuwenhuizen et al., MECHANISMS UNDERLYING THE INSULINOSTATIC EFFECT OF PEPTIDE YY IN MOUSE PANCREATIC-ISLETS, Diabetologia, 37(9), 1994, pp. 871-878
Citations number
36
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Peptide YY is an insulinostatic peptide which is released into the cir
culation from the intestinal mucosa upon food intake. Peptide YY is al
so co-stored with glucagon in the secretory granules of the pancreatic
alpha cells. We examined the mechanisms underlying the insulinostatic
effect of peptide YY in isolated mouse pancreatic islets. We found th
at peptide YY (0.1 nmol/l-1 mu mol/l) inhibited glucose (11.1 mmol/l)-
stimulated insulin secretion from incubated isolated islets, with a ma
ximal inhibition of approximately 70 % observed at a dose of 1 nmol/1
(p < 0.001). Also in perifused islets the peptide (1 nmol/l) inhibited
insulin secretion in response to 11.1 mmol/l glucose (p < 0.001). Fur
thermore, peptide YY inhibited glucose-stimulated cyclic AMP formation
(by 67 %, p < 0.05), and insulin secretion stimulated by dibutyryl cy
clic AMP (p < 0.01). In contrast, the peptide was without effect both
on the cytoplasmic Ca2+ concentration in dispersed mouse islet-cell su
spensions as measured by the FURA 2-AM technique, and on insulin relea
se in isolated islets, when stimulated by the protein kinase C-activat
or 12-O-tetradecanoyl phorbol 13-acetate. Finally, in pre-labelled per
ifused islets, peptide YY caused a small and transient increase in the
Rb-86(+) efflux (p < 0.001), but only in the absence of extracellular
Ca2+. We conclude that peptide YY inhibits glucose-stimulated insulin
secretion from isolated mouse islets by inhibiting two different step
s in the cyclic AMP cascade, that is, both the accumulation and the ac
tion of the cyclic nucleotide. In contrast, the data suggest that prot
ein kinase C, K+ channels, the cytoplasmic Ca2+ concentration or other
processes directly regulating the exocytosis are not involved in the
signal transduction underlying peptide YY-induced inhibition of insuli
n secretion.