Effect of somatostatin and two of its analogues on basal and arginine-stimulated insulin and glucagon secretion in the dog

Two analogues of somatostatin (d-Trp⁸,d-Cys¹⁴-somatostatin, and the octapeptide DesAA^{1,2,3,4,13,14},d-Trp⁸,GABA¹²-somatostatin) were compared with somatostatin using infusions, of 0.1 and 0.5 μg · kg^?1 · min^?1 in conscious dogs. Basal concentrations of insulin and glucagon were markedly and similarly lowered by all three somatostatin (SRIF) compounds at either dose. Arginine stimulation of insulin and glucagon secretion was entirely abolished by SRIF and by the octapeptide during infusion at 0.1 μg · kg^?1 · min^?1 but both hormones were only partly inhibited by d-Trp⁸,d-Cys¹⁴-SRIF. The higher dose (0.5 μg · kg^?1 · min^?1) of all three SRIF peptides lowered plasma insulin and glucagon before and during arginine stimulation. The recovery of plasma insulin and glucagon was delayed after discontinuation of the d-Trp⁸,d-Cys¹⁴-SRIF, and particularly after the octapeptide when compared with SRIF suggesting a longer duration of action of the analogues.The results did not confirm the previously suggested selective suppression of glucagon by d-Trp⁸,d-Cys¹⁴-SRIF. The new octapeptide appears to be promising for future clinical studies due to its potent inhibitory effect on insulin and glucagon, and its prolonged duration of action.