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

Abstract

Insulin-like growth factor-I (IGF-I) has been demonstrated to exert a nitrogen sparing effect, both experimentally and in patients after abdominal surgery. 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 the anabolic effects following GH has not been clarified. IGF-I influences glucose metabolism, both through its own specific receptor and by activating the insulin receptor, and has also been proposed to influence pancreatic islet secretion directly. In the present study, the postoperative effects of IGF-I on plasma levels of other gastrointestinal and pancreatic islet hormones and growth factors were measured in patients after abdominal surgery.Fifteen patients who were candidates for large bowel resection were randomly divided into two groups: IGF-Itreated (n=8) and placebo-treated (n=7). The IGF-I group received daily two s.c. injections of human recombinant IGF-I (80 µg/kg body weight) for five days, beginning on the morning of the first postoperative day. The other group received placebo injections. Fasting plasma levels of gastrointestinal growth factors (epidermal growth factor, transforming growth factor-, IGF-II), gastrointestinal hormones (gastrin, enteroglucagon, peptide YY), and islet hormones (insulin, islet amyloid polypeptide (IAPP) and pancreatic glucagon) were determined by RIA preoperatively 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 compared 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-treated patients remained unchanged (44 3 vs 45 4 pM). A similar pattern was observed for IAPP and cortisol concentrations. No differences in glucagon concentrations were seen.In conclusion, these results suggest that IGF-I does not influence production 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 -cell secretion could be direct or, alternatively, could involve an improvement in postoperative insulin resistance, perhaps by reducing serum cortisol.

Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Postoperative Muscle and Substrate Metabolism

“…In some studies IGF-1 given alone postoperatively showed no effect on nitrogen [26, 36]. IGF-1 treatment during 5 days postoperatively reduced plasma insulin and glucose levels, indicating an improved insulin sensitivity following surgery [35]. …”

“…In the present study a daily supply of GH (0.3 IU/kg/day) and IGF-1 (80  μ g/kg/day) was chosen since these amounts have shown effects on protein and substrate metabolism in earlier studies during the postoperative period [5, 11, 31–35]. …”

“…One group served as a control group ( n = 10), another group was given GH postoperatively (GH; n = 7) twice a day subcutaneously (0.15 IU/kg body weight/injection) and a third group (GH-IGF-1; n = 9) was given the same amount of GH and IGF-1 (40  μ g/kg body weight/injection) twice a day. This dosages has in earlier studies been shown to influence protein and substrate metabolism [5, 11, 31–35]. The study was designed to include 10 patients in each group, but when the use of growth hormone in catabolic patients was stopped by the results from the multicenter study on ICU patients [10] inclusion of patients in the present study was stopped.…”