Role of pancreatic somatostatin in determining glucagon response to arginine and morphine.
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)
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D004285:Dogs; D005934:Glucagon / Q000097:blood*; D007328:Insulin / Q000097:blood; D009020:Morphine / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*
D007328:Insulin; D013004:Somatostatin; D009020:Morphine; D005934:Glucagon; D001120:Arginine