Original ResearchBasic and Translational—Alimentary TractLoss of Glucagon-Like Peptide-2–Induced Proliferation Following Intestinal Epithelial Insulin-Like Growth Factor-1–Receptor Deletion
Section snippets
Animals
IE-igf1rKO mice were generated by crossing villin-Cre-ERT2+/0 and Igf1rflox/flox mice,22, 23, 24 both on a C57BL/6 background (Figure 1A). The resultant villin-Cre-ERT2+/0; Igf1rflox/+ offspring were mated to Igf1rflox/flox mice to generate the villin-Cre-ERT2+/0; Igf1rflox/flox (IE-igf1rKO) animals. Female villin-Cre-ERT2 breeders were avoided in F1 and F2 generations because of potential Cre excision from the maternal genome.25 Age- and sex-matched littermate Igf1rflox/flox and villin-Cre-ER
IGF-1R Deletion in IE-igf1rKO Mice
Polymerase chain reaction (PCR) analysis of IECs collected by laser capture microdissection 1 day after tamoxifen treatment showed the presence of the excised gene fragment (204 bp) only in cells from IE-igf1rKO mice as compared with control (Igf1rflox/flox) animals (Figure 1B). Densitometric analysis of the PCR products from 2 mice indicated approximately 85% recombination in IECs from the IE-igf1rKO mice. Moreover, quantitative reverse-transcription (qRT)-PCR for IGF-1R mRNA in jejunal mucosa
Discussion
Based on the localization of both IGF-130, 31, 32, 33, 34 and the GLP-2R11 in the intestinal subepithelial myofibroblasts that subtend the crypt epithelium, as well as on expression of the IGF-1R on the basolateral membrane of crypt IECs,30, 35 we have proposed a role for the IEC IGF-1R in GLP-2–mediated SI proliferation.3, 4 Moreover, we recently showed that GLP-2 not only stimulates IGF-1 secretion from cultured fetal rat intestinal cells,13 but also increases IGF-1 mRNA transcript levels in
Acknowledgments
The authors thank Dr Sylvie Robine (Institut Curie-Centre National de la Recherche Scientique, Paris, France) for the kind gift of the villin-cre mice, and Mr Angelo Izzo for technical support. The authors also thank Mr Brent Steer and Dr Phil Marsden (University of Toronto) for assistance with laser capture microdissection procedures.
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2020, Journal of Dairy ScienceCitation Excerpt :Of particular interest to the current study is the oral delivery of IGF-1 in colostrum (Pakkanen and Aalto, 1997; Blum and Hammon, 2000) to the neonatal calf by its small intestine-targeted mitogenic capacity to increase epithelial cell proliferation (MacDonald, 1999; Shen et al., 2004). Because the mitogenic action of IGF-1 can be enhanced by GLP-2 (Dubé et al., 2006; Rowland et al., 2011; Leen et al., 2011), these 2 hormones were promising targets to determine their relationship to neonatal intestinal development and postnatal nutrient consumption. Yet, study findings did not support the hypothesis that elevated plasma GLP-2 and serum IGF-1 concentrations would reflect and coincide with enhanced intestinal development by COL compared with MIX or WM feeding.
Conflicts of interest This author discloses the following: Patricia Brubaker has received consulting fees from Glaxo-Smith-Kline and Regeneron. The remaining authors disclose no conflicts.
Funding Katherine Rowland was supported by a Doctoral Research Award from the Canadian Institutes of Health Research in partnership with the Canadian Digestive Health Foundation, and by a Banting and Best Diabetes Centre Graduate Studentship, University of Toronto; Shivangi Trivedi and Ken Wan were supported by Canadian Association of Gastroenterology Summer Studentships; and Patricia Brubaker was supported by the Canada Research Chairs Program. These studies were supported by an operating grant from the Canadian Institutes of Health Research (#MOP-9940 to PLB); and by the National Institutes of Health (RO1 #DK67536; to RNK).