Differential effects of somatostatin analogues on alpha- and beta-cells of the pancreas.

We examined the effect of somatostatin (SS) and its analogues on basal insulin and glucagon output from the right lobe of the in situ canine pancreas. Somatostatin (0.17 and 1.7 microgram/min, iv) significantly inhibited insulin (delta = -48 +/- 9% and delta = -88 +/- 3%) and glucagon (delta = -13 +/- 16%, P = NS and delta = -55 +/- 8%). Des-Asn5-SS Significantly inhibited insulin (delta = -40 +/- 9% and delta = -92 +/- 3%) but not glucagon (delta = +35 +/- 18% and delta = +4 +/- 12%). Likewise, [D-Ser13]-SS significantly inhibited insulin (delta = -40 +/- 14% and delta = -71 +/- 8%) with only slight inhibition of glucagon (delta = +26 +/- 15%, P = NS and delta = -16 +/- 6%, P less than 0.05). In contrast, [D-Cys14]-SS significantly inhibited both inhibited both insulin and glucagon. We conclude that structural changes of cyclic somatostatin can dissociate its ability to inhibit pancreatic insulin and glucagon secretion. Because the putative receptors on the pancreatic alpha- and beta-cell appear to recognize different configurations of the somatostatin molecule, it is suggested that the receptors themselves are different.