Effect of a cyclic hexapeptide analog (L363,586) of somatostatin on the function of pancreas grafts in dogs.
Complications related to the exocrine secretions cause some pancreas grafts to fail in the early postoperative period. Somatostatin inhibits exocrine secretion, as well as insulin and glucagon release. L363,586 is a cyclic hexapeptide analog of somatostatin that is 50 to 100 times more potent than the native hormone in inhibiting islet hormone release. In a preliminary experiment in which permanent fistulas were created in two dogs, we demonstrated that L363,586 (0.3 micrograms/kg/60 min) results in a fourfold decrease in pancreatic exocrine secretion when measured for 210 min following a beef meal. In a separate experiment, five totally pancreatectomized dogs who received segmental pancreas autografts with pancreaticoductocystostomy 10 months previously had L363,586 (0.3 micrograms/kg/hr) administered by the Alzet osmotic pump subcutaneously for 7 days. Mean (+/-SE) daily serum amylase activity (IU/dl) during the week before the implant was 78 +/- 3, during the week of infusion was 65 +/- 2 (P less than 0.001), and during the week afterward was 76 +/- 2. In a prospective experiment, 12 totally pancreatectomized dogs received segmental pancreas autografts with anastomosis of the graft vessels to the iliac vessels and of the pancreatic duct to the bladder. L363,586 was administered by osmotic pump for 7 days to seven dogs at a dose of 0.3 micrograms/kg/hr. Mean (+/-SE) daily serum amylase levels at 1, 2, and 3 weeks posttransplant were 223 +/- 17, 81 +/- 3, and 82 +/- 5 in the L363,586-treated dogs and 229 +/- 18, 108 +/- 5, and 90 +/- 5 in the five untreated dogs (P less than 0.001 at 2 weeks).(ABSTRACT TRUNCATED AT 250 WORDS)
T
T
Liu
D E
DE
Sutherland
P L
PL
Chinn
J S
JS
Najarian
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004285:Dogs; D006728:Hormones / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D010179:Pancreas / Q000187:drug effects; D016035:Pancreas Transplantation; D010189:Pancreatic Juice / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D012636:Secretory Rate / Q000187:drug effects; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology
D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D010456:Peptides, Cyclic; D013004:Somatostatin; C040968:seglitide; D000681:Amylases