| Nutritional and hormonal regulation of intestinal growth is incompletely understood. We hypothesized nutrition and hormones stimulate adaptation of the small intestine in association with alterations in enterocyte kinetics. Our objective was to assess jejunal mucosal composition and enterocyte proliferation, apoptosis, and migration in association with total parenteral nutrition (TPN), mid small bowel resection, endogenous glucagon-like peptide-2 (GLP-2) responses, and/or insulin-like growth factor-I (IGF-I) administration in rats.; Elimination of exogenous luminal nutrients due to TPN induced significant jejunal mucosal hypoplasia in association with reduced enterocyte proliferation and increased apoptosis in the crypt and bottom-half of the villus in rats with intact bowel. A lack of increased apoptosis in the top half of the villus suggests enterocyte loss from the villi tips is not apoptosis-mediated.; Mid small bowel resection stimulated jejunal mucosal hyperplasia during TPN, independent of parenteral lipid. This demonstrates that exogenous luminal nutrients are not essential for resection-induced intestinal adaptation although the presence of luminal nutrients enhanced the adaptive response. The resection-induced hyperplasia during TPN was associated with stimulation of enterocyte proliferation, inhibition of apoptosis, and enhanced enterocyte migration whereas during oral feeding, adaptation was associated with an increase in proliferation and no significant change in apoptosis.; Endogenous bioactive GLP-2, an intestinotrophic peptide derived from the proglucagon gene, was transiently elevated following resection in the absence of exogenous luminal nutrients. This supports a significant role for endogenous GLP-2 in stimulating the adaptive response to resection in TPN rats. Exogenous IGF-I augmented resection-induced adaptive hyperplasia. This was reflected in an increase in enterocyte proliferation, an expansion of the proliferative compartment in the crypt, and no further decrease in enterocyte apoptosis or increase in enterocyte migration beyond the effects of resection alone.; In conclusion, this research demonstrates for the first time in TPN-resected rats that: (1) intestinal adaptation occurs in the absence of exogenous luminal nutrients, (2) endogenous plasma bioactive GLP-2 is associated with the adaptive response, and (3) IGF-I enhances resection-induced hyperplasia by increasing enterocyte proliferation. Further elucidation of the nutritional and hormonal factors regulating intestinal adaptation may lead to improved treatments for patients with compromised intestinal integrity. |
