期刊
DIGESTIVE DISEASES AND SCIENCES
卷 49, 期 11-12, 页码 1731-1737出版社
SPRINGER
DOI: 10.1007/s10620-004-9561-8
关键词
gastrointestinal hormones; monosaccharide transport proteins; intestinal epithelium; diurnal rhythm; gene expression regulation
资金
- NIDDK NIH HHS [DK47326, DK02786, DK54399] Funding Source: Medline
Glucagon-like peptide 2 (GLP-2) is a 33-amino acid gut peptide that leads to villus hyperplasia and altered gene expression. We examined the effect of chronically administered GLP-2 on diurnal gene expression rhythms using the Na+/glucose cotransporter 1 (SGLT1) as the index. Animals were treated with [Gly(2)]GLP-2 (twice daily; 1 mug/g body weight) or vehicle (control) for 10 days. Rats were killed at either 3 hr or 9 hr after light onset (ZT3 and ZT9, respectively), an interval during which SGLT1 expression exhibits a robust induction. SGLT1 mRNA expression was assessed by Northern blotting and in situ hybridization. SGLT I protein was examined by immunofluorescence and Western blotting. Tissues from GLP-2-treated rats had increased villus height, crypt depth, and proliferation index (P<0.05). GLP-2 administration did not alter the diurnal increase in mRNA levels of SGLT1, GLUT2, or GLUT5. However, in GLP-2-treated rats, the SGLT1 protein amount increased at both ZT3 and ZT9. Moreover, SGLT1 was preferentially localized to the apical membranes in this group. GLP-2 does not adversely affect the diurnal expression rhythm of SGLT I and appears to increase membrane expression of the protein. These biological actions of GLP-2 may contribute to its therapeutic value in intestinal diseases.
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