Gastrointestinal growth factors and pancreatic islet hormones during postoperative IGF-I supplementation in man

Insulin-like growth factor-I (IGF-I) has been demonstrated to exert a nitro gen sparing effect, both experimentally and in patients after abdominal sur gery. IGF-I is a major mediator for the anabolic effects of growth hormone (GH). Whether elevated circulating IGF-I levels are the sole mediator of th e anabolic effects following GH has not been clarified. TGF-I influences gl ucose metabolism, both through its own specific receptor and by activating the insulin receptor, and has also been proposed to influence pancreatic is let secretion directly. In the present study, the postoperative effects of IGF-I on plasma levels of other gastrointestinal and pancreatic islet hormo nes and growth factors were measured in patients after abdominal surgery. Fifteen patients who were candidates for large bowel resection were randoml y divided into two groups: IGF-I-treated (n=8) and placebo-treated (n=7). T he IGF-I group received daily two s.c. injections of human recombinant IGF- I (80 mug/kg body weight) for five days, beginning on the morning of the fi rst postoperative day. The other group received placebo injections. Fasting plasma levels of gastrointestinal growth factors (epidermal growth factor, transforming growth factor-alpha, IGF-II), gastrointestinal hormones (gast rin, enteroglucagon, peptide YY), and islet hormones (insulin, islet amyloi d polypeptide (IAPP) and pancreatic glucagon) were determined by RIA preope ratively and after five days of treatment. No significant effects of IGF-I on other growth factors or gastrointestinal hormones were seen. A marked increase in plasma insulin postoperatively co mpared with the preoperative levels (42 +/- 3 vs 61 +/- 5 pM, P<0(.)05) was seen in the placebo group, whereas the postoperative levels in the IGF-I-t reated patients remained unchanged (44 +/- 3 vs 45 +/- 4 pM). A similar pat tern was observed for IAPP and cortisol concentrations. No differences in g lucagon concentrations were seen. In conclusion, these results suggest that IGF-I does not influence producti on of other gastrointestinal hormones thought to be involved in alimentary growth or pancreatic glucagon. In contrast, IGF-I caused a marked reduction of insulin and IAPP secretion. The inhibition of <beta>-cell secretion cou ld be direct or, alternatively, could involve an improvement in postoperati ve insulin resistance, perhaps by reducing serum cortisol.