Somatostatin antagonism prevents elemental diet-induced intestinal atrophy in the rat

Somatostatin is a peptide with known antiproliferative effects on the intestine. The aim of the present work was to determine whether somatostatin (SST) antagonism reduces elemental diet-induced intestinal atrophy in the rat. Male Wistar rats were fed a standard diet and treated for seven days with either continuous infusion of saline or low and high doses of a putative somatostatin antagonist; another group was given a SST antagonist in a pulsatile high dose. All these groups received an elemental diet to induce gut mucosa atrophy. Rats were killed and samples were obtained for morphometric and proliferative measurements of the intestine and for SST and insulin-like growth factor-1 (IGF-1) level determination. The elemental diet decreased mucosal length and proliferation. Pulsatile administration of SST antagonist improved or prevented both effects, whereas continuous SST antagonist delivery prevented decreased crypt proliferation induced by the elemental diet. Somatostatin plasma levels were lowest in rats receiving pulsatile administration of SST antagonist. In conclusion, somatostatin antagonism increases proliferation in the intestinal mucosa, improving elemental diet-induced intestinal atrophy; however, morphological growth is not affected.