IGF Binding Protein-4 is Required for the Growth Effects of Glucagon-Like Peptide-2 in Murine Intestine
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- Kaori Austin
- Departments of Physiology (K.A., N.A.I., P.L.B.), University of Toronto, Toronto, Ontario, Canada M5S 1A8
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- Nuvair A. Imam
- Departments of Physiology (K.A., N.A.I., P.L.B.), University of Toronto, Toronto, Ontario, Canada M5S 1A8
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- John E. Pintar
- Department of Neuroscience and Cell Biology (J.E.P.), Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854
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- Patricia L. Brubaker
- Departments of Physiology (K.A., N.A.I., P.L.B.), University of Toronto, Toronto, Ontario, Canada M5S 1A8
抄録
<jats:p>Glucagon-like peptide-2 (GLP-2) is an enteroendocrine hormone that stimulates the growth of the intestinal epithelium. We have previously demonstrated that GLP-2 exerts its intestinotropic effect through an indirect mechanism that requires both IGF-1 and the intestinal epithelial IGF-1 receptor. However, the biological activity of IGF-1 is modulated by IGF binding proteins (IGFBPs), including IGFBP-4, which is highly expressed in the intestine. To determine the role of IGFBP-4 in the tropic effects of GLP-2, IGFBP-4 knockout (KO) and control mice were treated with degradation-resistant GLP-2 or vehicle for 10 days. Comparable levels of IGFBP-1–3/5–7 mRNAs were observed in the intestinal mucosa of all animals. IGFBP-4 KO mice had greater small intestinal weight and length, and deeper crypts (P < .05) as compared with controls, suggesting that IGFBP-4 has an inhibitory role in basal intestinal growth. However, small intestinal weight, crypt-villus height and crypt cell proliferation increased in response to GLP-2 in control mice (P < .05), and these changes were abrogated with IGFBP-4 KO. In contrast, pregnancy-associated plasma protein-A KO mice, which have increased levels of circulating IGFBP-4, demonstrated a normal intestinotropic response to GLP-2. Finally, GLP-2 treatment of control mice significantly increased IGFBP-4 mRNA expression in the jejunal mucosa (P < .05), a finding that was recapitulated by GLP-2 treatment of fetal rat intestinal cells in culture (10−8M for 2 h; P < .05). Collectively, these results indicate that the IGF-I-modulating protein, IGFBP-4, exerts a negative effect on basal intestinal growth but plays a positive regulatory role in the intestinotropic actions of GLP-2.</jats:p>
収録刊行物
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- Endocrinology
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Endocrinology 156 (2), 429-436, 2014-12-16
The Endocrine Society
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キーワード
詳細情報 詳細情報について
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- CRID
- 1362544418459037184
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- ISSN
- 19457170
- 00137227
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- データソース種別
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- Crossref