Requirement for the intestinal epithelial insulin‐like growth factor‐1 receptor in the intestinal responses to glucagon‐like peptide‐2 and dietary fat
| Autor: | Derek S. Tsang, Arjuna Srikrishnaraj, Patricia L. Brubaker, Melanie A. Markovic |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Enterocyte medicine.medical_treatment CD36 Biochemistry Receptor IGF Type 1 Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences Insulin-like growth factor 0302 clinical medicine Internal medicine Glucagon-Like Peptide 2 Genetics medicine Animals Intestinal Mucosa Receptor Molecular Biology Protein kinase B Cell Proliferation Mice Knockout biology Chemistry Glucagon-like peptide-2 Dietary Fats Mice Inbred C57BL Jejunum 030104 developmental biology medicine.anatomical_structure Endocrinology biology.protein Female Signal transduction 030217 neurology & neurosurgery Signal Transduction Biotechnology Hormone |
| Zdroj: | The FASEB Journal. 34:6628-6640 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.202000169r |
| Popis: | The intestinal hormone, glucagon-like peptide-2 (GLP-2), enhances the enterocyte chylomicron production. However, GLP-2 is known to require the intestinal-epithelial insulin-like growth factor-1 receptor (IE-IGF-1R) for its other actions to increase intestinal growth and barrier function. The role of the IE-IGF-1R in enterocyte lipid handling was thus tested in the GLP-2 signaling pathway, as well as in response to a Western diet (WD). IE-IGF-1R knockout (KO) and control mice were treated for 11 days with h(GLY2 )GLP-2 or fed a WD for 18 weeks followed by a duodenal fat tolerance test with C14 -labeled triolein. Human Caco-2BBE cells were treated with an IGF-1R antagonist or signaling inhibitors to determine triglyceride-associated protein expression. The IE-IGF-1R was required for GLP-2-induced increases in CD36 and FATP-4 in chow-fed mice, and for expression in vitro; FATP-4 also required PI3K/Akt. Although WD-fed IE-IGF-1R KO mice demonstrated normal CD36 expression, the protein was incorrectly localized 2h post-duodenal fat administration. IE-IGF-1R KO also prevented the WD-induced increase in MTP and decrease in APOC3, increased jejunal mucosal C14 -fat accumulation, and elevated plasma triglyceride and C14 -fat levels. Collectively, these studies elucidate new roles for the IE-IGF-1R in enterocyte lipid handling, under basal conditions and in response to GLP-2 and WD-feeding. |
| Databáze: | OpenAIRE |
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