Role of pancreatic somatostatin in determining glucagon response to arginine and morphine
Klaff, L.J.; Taborsky, G.J.
American Journal of Physiology 252(6 Pt 1): E751-E755
1987
ISSN/ISBN: 0002-9513 PMID: 2884887 Document Number: 297978
It has been proposed that pancreatic somatostatin (SS) tonically inhibits pancreatic glucagon secretion. In keeping with this hypothesis, we have previous 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 on 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. These data suggest that these two agents elicit a glucagon response by different mechanisms and that both are influenced by pancreatic SS, supporting the hypothesis that pancreatic SS is an important intraislet regulator of glucagon secretion.