An in vivo model for testing inhibition of arginine-induced insulin and glucagon release by somatostatin analogs.

An animal model for testing the in vivo potency of somatostatin analogs in inhibiting the release of insulin and glucagon is described. The secretion of these pancreatic hormones was stimulated in rat by infusion of arginine. The plasma insulin level increased almost to a maximum after an infusion of 10 min, while plasma glucagon rose more slowly, reaching its maximum only after a 30 min infusion. Concomitant infusion of graded doses of somatostatin (2.5, 10, 40 and 160 microgram/100 g BW) for 30 min inhibited both insulin and glucagon release in a dose-dependent manner, enabling us to test somatostatin analogs for insulin and glucagon-suppressive activity in a semi-quantitative manner. Using this animal model, 3 analogs of somatostatin [D-Cys14]-, [Ala2, D-Cys14]- and [D-Trp8, D-Cys14]somatostatin were tested in a 4-point assay. They all showed dissociated activity in inhibiting the secretion of glucagon more than that of insulin.