Regulation and localization of the insulin-like growth factor system in small bowel during altered nutrient status

Abstract

Insulin-like growth factor-I (IGF-I) may regulate small bowel growth. Analyses here in ad libitum-fed, fasted, and refed rats demonstrate that during fasting and refeeding changes in jejunal mass correlate with changes in serum IGF-I and jejunal IGF-I mRNAs. These data indicate that circulating and locally expressed IGF-I contribute to nutrient regulation of jejunal mass. During refeeding, jejunal IGF binding protein 3 (IGFBP-3) mRNA abundance was reduced relative to that of IGF-I, possibly amplifying enterotrophic actions of IGF-I. Localization of IGFBP-3 to subepithelial cells in lamina propria of jejunum indicates that IGFBP-3 derived from lamina propria may modulate IGF-I action on adjacent epithelium. Ileum differed from jejunum in that refeeding did not increase bowel mass or IGF-I mRNA to ad libitum values. Differences in exposure to luminal nutrient may underlie distinct responses of the two segments. Rats fed elemental diet intravenously showed reduced jejunal mass but not reduced jejunal IGF-I mRNA compared with rats fed oral elemental diet. Elemental nutrient given intravenously or orally therefore does not differ in effects on jejunal IGF-I expression. Complex luminal nutrient may, however, regulate jejunal IGF-I expression.

IGF Binding Protein-3 Treatment Alters Intestinal Cell Proliferation But Not Body Weight of Adult Cystic Fibrosis Transmembrane Conductance Regulator Deficient Mice

“…Specifically, the intestinal phenotype of CF mice histologically resembles that of rats after major small bowel resection wherein changes in the ileum include muscle wall hypertrophy and villus enlargement (21). Igfbp-3 mRNA levels in the intestine are decreased after major small bowel resection (22) or after postfast refeeding, where the decrease coincides with a similar growth response in the intestinal mucosa (10). Second, Gillingham et al (23) reported increased expression of Igf-1 and Igfbp-5, which were also more highly expressed in the CF intestine, in sections of intestinal growth of a jejunoileal resection model.…”

“…Igf-I is regulated by a family of proteins, known as the IGF-binding proteins (IGFBPs), which modulate Igf-I action either by presenting Igf-I to its receptor or by sequestering the peptide and reducing receptor interaction (8). Igfbp-3 accounts for 80% of IGF binding in the circulation (9) and may modulate Igf-I action in the intestine (10). Independent of the Igf-I interaction, increased levels of Igfbp-3 have been shown to inhibit the proliferation of intestinal smooth muscle cells (11) and to induce apoptosis in colonic adenoma-derived cells (12).…”

Apolipoprotein E knockout mice have accentuated malnutrition with mucosal disruption and blunted insulin-like growth factor I responses to refeeding

“…Early weaning, altered nutrient status, and changing of diets can severely affect patterns of early growth and related hormone secretion, and refeeding may effectively restore normal physiologic and physical development [50,51] Circulating growth factors, such as IGF-1, have been implicated in the control of the intestinal epithelial proliferation and influencing cell migration and differentiation on in vitro and in vivo models of intestinal healing [33], effects that may be stimulated and regulated by critical nutrients [52] upon refeeding.…”

Trefoil peptide expression and goblet cell number in rat intestine: effects of KGF and fasting-refeeding

“…Nutritional status also regulates expression of various endogenous intestinal growth factors, including insulinlike growth factor-I and KGF and its receptor (9,44,(47)(48)(49). However, there have been few studies on nutrient regulation of intestinal goblet cells (6,30,35,37) or TFF peptide expression.…”