Selective effect of some somatostatin analogs on glucagon as opposed to insulin release in rats in vivo

Cyclic somatostatin, at a dose of 700 but not 70 ng/kg/min, inhibited arginine-induced insulin and glucagon release as well as glucose stimulated insulin release in rats in vivo. Three somatostatin (S-S) analogs (D-Cys¹⁴-S-S, D-Trp⁸-D-Cys¹⁴-S-S and Ala²-D-Trp⁸-D-Cys¹⁴-S-S), D-Trp₈-D-Cys₁4-S-S and Ala₂-D-Trp₈-D-Cys₁4-S-S), at a dose of 70 ng/kg/min, suppressed arginine-induced glucagon but not insulin release. At the same dose, the first two of these analogs had no effect on glucose-induced insulin release, while the third one, Ala²-D-Trp⁸-D-Cys¹⁴-somatostatin, enhanced insulin release induced by glucose. A fourth analog, D-Trp⁸-somatostatin, was more potent than somatostatin with regard to arginine stimulated insulin and glucagon release, and equipotent with somatostatin with respect to glucose stimulated insulin release. These studies show, firstly, the inhibitory effect of somatostatin analogs on arginine induced insulin release may be different from that when glucose is used as a stimulant and, secondly, that Ala²-D-Trp⁸-D-Cys¹⁴-somatostatin inhibits arginine-induced glucagon release while enhancing insulin release on glucose stimulation.