TY - JOUR
T1 - Effect of glucagon-like peptide-2 (GLP-2) on diurnal SGLT1 expression
AU - Ramsanahie, Anthony P.
AU - Berger, Urs V.
AU - Zinner, Michael J.
AU - Whang, Edward E.
AU - Rhoads, David B.
AU - Ashley, Stanley W.
N1 - Funding Information:
This work was supported by NIH Grants DK02786 (E.E.W.), DK54399 (D.B.R.), and DK47326 (S.W.A.). The authors gratefully acknowledge Bruce A. Hirayama (UCLA School of Medicine, Los Angeles, CA) for providing rabbit anti-rat SGLT1 antibodies and the expert technical assistance of Lihua Zhang and Jan Rounds.
PY - 2004/11
Y1 - 2004/11
N2 - 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 [Gly2]GLP-2 (twice daily; 1 μg/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. SGLT1 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 SGLT1 and appears to increase membrane expression of the protein. These biological actions of GLP-2 may contribute to its therapeutic value in intestinal diseases.
AB - 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 [Gly2]GLP-2 (twice daily; 1 μg/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. SGLT1 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 SGLT1 and appears to increase membrane expression of the protein. These biological actions of GLP-2 may contribute to its therapeutic value in intestinal diseases.
KW - Diurnal rhythm
KW - Gastrointestinal hormones
KW - Gene expression regulation
KW - Intestinal epithelium
KW - Monosaccharide transport proteins
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U2 - 10.1007/s10620-004-9561-8
DO - 10.1007/s10620-004-9561-8
M3 - Article
C2 - 15628694
AN - SCOPUS:13644267769
SN - 0163-2116
VL - 49
SP - 1731
EP - 1737
JO - Digestive diseases and sciences
JF - Digestive diseases and sciences
IS - 11-12
ER -