Insulin Modulates Cellular Proliferation in Developing Human Jejunum and Colon

Abstract

Several lines of evidence suggest an important role for insulin in the regulatory mechanism of rodent small intestinal development. To investigate its potential implication in human gut, the immunofluorescent localization of insulin receptors (IR) and the influence of insulin (30 µU or 3 mU/ml) on [³H]-thymidine incorporation and on lactase and alkaline phosphatase activities were studied in fetal jejunum and colon (14–19 weeks). We demonstrate the early presence of IR, mainly detected in the basolateral portion of enterocytes and colonocytes along the crypt-villus axis. Insulin increased [³H]-thymidine incorporation as well as epithelial labeling indices in cultured explants from jejunum and colon without affecting enzymic activities. This study establishes, for the first time, that insulin stimulates proliferation of epithelial cells expressing IR in both segments without affecting brush border hydrolases in the developing human gut.

Increased Transduction of Human Intestinal Epithelial Cells by Adenoviral Vectors in Inflammatory Bowel Disease

“…Human intestinal explants32 have been used for a variety of studies including the study of intestinal lipid transport,33 the effect of insulin on epithelial cell proliferation,34 and the synthesis of brush border membrane proteins 35. Explants offer the opportunity to study epithelial cell biology in the context of normal tissue components and organization.…”

Developmental Regulation of Intestinal Epithelial Hydrolase Activity in Human Fetal Jejunal Xenografts Maintained in Severe-Combined Immunodeficient Mice

“…Signals derived from luminal amniotic fluid may also contribute to the development of enzyme activities in utero (44), possibly mediated by specific growth factors. Organ culture studies of human fetal intestine in defined tissue culture medium have demonstrated differential effects of hydrocortisone, insulin, and epidermal growth factor in regulating hydrolase expression, apolipoprotein and lipoprotein secretion, and cellular proliferation (45)(46)(47)(48)(49). However, the implication of these important findings to tissue development in utero are somewhat limited by the current inability to perform long-term in vitro experiments on late-gestational fetal intestine.…”

Insulin-like growth factor and insulin receptors in intestinal mucosa of neonatal calves

“…During the postnatal period insulin-like growth factor (IGF)-I becomes more important than IGF-II (Breier et al 2000, Butler & LeRoith 2001. The somatotropic axis and especially IGFs, besides insulin, is involved in GIT development and especially in proliferation and maturation of enterocytes (Laburthe et al 1988, Schober et al 1990, Odle et al 1996, MacDonald 1999, Menard et al 1999. It has been demonstrated that IGF-II and insulin are involved in the mechanisms governing the differentiation of intestinal epithelium while IGF-I is mostly associated with crypt cell proliferation (Jehle et al 1999).…”