SYSTEMICALLY BUT NOT OROGASTRICALLY DELIVERED INSULIN-LIKE-GROWTH-FACTOR (IGF)-I AND LONG [ARG(3)]IGF-I STIMULATES INTESTINAL DISACCHARIDASE ACTIVITY IN 2 AGE-GROUPS OF SUCKLING RATS

The growth mitogenic properties of IGF-I on tissues of the gastrointes tinal tract are well established; however, IGF effects on enzyme matur ation are less clear. To test whether IGF-I peptide administration sti mulates disaccharidase activity, we administered IGF-I or the more pot ent analog, long [Arg(3)]IGF-I, at doses ranging between 2 and 12.5 mu g g(-1) d(-1) to suckling Wistar rat pups by either continuous s.c. i nfusion or by three times daily orogastric gavage. Peptides were admin istered for approximately 6 d starting on d 6 or 12 postpartum with si x to nine rats per group. The results of the study demonstrated that s ystemically but not orally administered IGF-I stimulated duodenal wet tissue weight (up to 85%) and length (up to 36%). Enzyme maturation wa s assessed by measuring disaccharidase biochemically in tissue homogen ates. Enzyme activity was also localized histocytochemically in cryost at-sectioned duodenum. After systemic infusion of IGF-I, intestinal la ctase activity increased proportional to mucosal mass in both age grou ps. Systemic infusion of the more potent analog, long [Arg3]IGF-I, pre cociously induced the decline in lactase activity and accelerated the appearance of sucrase activity in the rat pups infused during the late r suckling period. These findings indicate that enzyme maturation can be accelerated by systemically derived IGF-I peptides. Orogastrically IGF-I peptides, delivered at pharmacologic doses, did not affect intes tinal growth or digestive enzyme maturation in suckling rat pups treat ed between 6 and 18 d postpartum, indicating the efficacy of IGF-I pep tides may depend on the route of delivery and postnatal age of the rec ipient.