AJP - Endocrinology and Metabolism, Vol 252, Issue 6 E751-E755, Copyright © 1987 by American Physiological Society
Role of pancreatic somatostatin in determining glucagon response to arginine and morphine
L. J. Klaff and G. J. Taborsky Jr
It has been proposed that pancreatic somatostatin (SS) tonically inhibits
pancreatic glucagon secretion. In keeping with this hypothesis, we have
previously shown that infusion of a nonimmunoreactive analogue of SS,
[D-Ala5,D-Trp8]somatostatin (SSa), which in low doses inhibits SS secretion
without inhibiting glucagon or insulin secretion, is associated with a
large increase in glucagon and small increase in insulin secretion.
Although direct stimulation of the alpha- and beta-cells by the analogue
could not be excluded, high doses of the analogue appeared to inhibit
insulin and glucagon secretion. These data therefore suggested that the
effect of the analogue on insulin and glucagon secretion was indirect and
due to reduction of tonic inhibition on the alpha- and beta-cells by SS. If
pancreatic SS is an important regulator of glucagon secretion, then
alterations in pancreatic SS should influence the glucagon response to
secretagogues. Therefore, in the present study, we have examined the
glucagon response to two different stimuli, arginine and morphine, either
before or during suppression of pancreatic SS secretion. Intravenous
injection of arginine produced a rapid increase of pancreatic glucagon
output from the in vivo dog pancreas. When basal pancreatic SS output was
suppressed by infusion of SSa, arginine injection produced a twofold larger
glucagon response. Infusion of morphine directly into the pancreatic artery
of the dog decreased pancreatic SS output and increased pancreatic glucagon
output. When SS was suppressed by SSa infusion, morphine did not further
suppress pancreatic SS secretion and the glucagon response to morphine was
abolished.(ABSTRACT TRUNCATED AT 250 WORDS)
