| First Author | Baraille F | Year | 2015 |
| Journal | Diabetes | Volume | 64 |
| Issue | 8 | Pages | 2744-56 |
| PubMed ID | 25829452 | Mgi Jnum | J:246317 |
| Mgi Id | MGI:5923702 | Doi | 10.2337/db14-0993 |
| Citation | Baraille F, et al. (2015) Glucose Tolerance Is Improved in Mice Invalidated for the Nuclear Receptor HNF-4gamma: A Critical Role for Enteroendocrine Cell Lineage. Diabetes 64(8):2744-56 |
| abstractText | Intestine contributes to energy homeostasis through the absorption, metabolism, and transfer of nutrients to the organism. We demonstrated previously that hepatocyte nuclear receptor-4alpha (HNF-4alpha) controls intestinal epithelium homeostasis and intestinal absorption of dietary lipids. HNF-4gamma, the other HNF-4 form highly expressed in intestine, is much less studied. In HNF-4gamma knockout mice, we detect an exaggerated insulin peak and improvement in glucose tolerance during oral but not intraperitoneal glucose tolerance tests, highlighting the involvement of intestine. Moreover, the enteroendocrine L-type cell lineage is modified, as assessed by the increased expression of transcription factors Isl1, Foxa1/2, and Hnf4a, leading to an increase of both GLP-1-positive cell number and basal and stimulated GLP-1 plasma levels potentiating the glucose-stimulated insulin secretion. Using the GLP-1 antagonist exendin (9-39), we demonstrate a direct effect of GLP-1 on improved glucose tolerance. GLP-1 exerts a trophic effect on pancreatic beta-cells, and we report an increase of the beta-cell fraction correlated with an augmented number of proliferative islet cells and with resistance to streptozotocin-induced diabetes. In conclusion, the loss of HNF-4gamma improves glucose homeostasis through a modulation of the enteroendocrine cell lineage. |
