Diabetes, Vol 38, Issue 12 1534-1538, Copyright © 1989 by American Diabetes Association
Effects of glucagonlike peptide I-(7-36) on release of insulin, glucagon, and somatostatin by rat pancreatic islet cell monolayer cultures
DA D'Alessio, WY Fujimoto and JW Ensinck
Department of Medicine, University of Washington, Seattle 98195.
Glucagonlike peptide I (GLP-I-(7-36] is cleaved from proglucagon in ileal
epithelial cells and increases in human plasma after nutrient ingestion.
This peptide has been shown to stimulate insulin secretion in vitro and in
vivo and thus potentially acts as an incretin. To characterize its action
on islet cells, the release of insulin, glucagon, and somatostatin by rat
pancreatic islet monolayer cultures at varying concentrations of
GLP-I-(7-36) was measured. The interaction of GLP-I-(7-36) with nutrient
substrates was assessed by adding amino acids and differing glucose
concentrations to the cultures. Islet cell cultures (n = 5) were incubated
for 1 h in medium containing 1.67 or 16.7 mM glucose or 1.67 mM glucose
supplemented with amino acids and GLP-I-(7-36) at 10(-13)-10(-7) M. Hormone
release was compared with control cultures containing no GLP-I-(7-36);
1.67-16.7 mM glucose with and without GLP-I-(7-36) at 10(-11) M; and 1.67,
3.3, 8.3, or 11.1 mM glucose alone or supplemented with amino acids,
GLP-I-(7-36) 10(-11) M, or both amino acids and GLP-I-(7-36). In medium
with 1.67 or 16.7 mM glucose or 1.67 mM glucose and amino acids,
GLP-I-(7-36) increased insulin secretion two- to threefold over control at
concentrations of 10(-9), 10(-11), and 10(-12) M, respectively. In medium
with increasing concentrations of glucose, GLP-I-(7-36) at 10(-11) M
significantly increased insulin secretion at glucose concentrations greater
than or equal to 3.34 mM.(ABSTRACT TRUNCATED AT 250 WORDS)