Effect of glucagon-like peptide-2 (GLP-2) on diurnal SGLT1 expression.
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; 1microg/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.
Ramsanahie
Anthony P
AP
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Berger
Urs V
UV
Zinner
Michael J
MJ
Whang
Edward E
EE
Rhoads
David B
DB
Ashley
Stanley W
SW
D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D051273:Glucose Transporter Type 2; D051296:Glucose Transporter Type 5; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008027:Light; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis*; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1; D013997:Time Factors
D005768:Gastrointestinal Hormones; D053767:Glucagon-Like Peptide 2; D051273:Glucose Transporter Type 2; D051296:Glucose Transporter Type 5; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D010455:Peptides; D012333:RNA, Messenger; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D004763:Glucagon-Like Peptides