Intestinal function in mice with small bowel growth induced by glucagon-like peptide-2.
Glucagon-like peptide-2 (GLP-2) stimulates small intestinal growth through induction of intestinal epithelial proliferation. To examine the physiology of GLP-2-induced bowel, mice were treated with GLP-2 (2.5 micrograms) or vehicle for 10 days. Small intestinal weight increased to 136 +/- 2% of controls in GLP-2-treated mice, in parallel with 1.4 +/- 0.1- and 1.9 +/- 0.5-fold increments in duodenal RNA and protein content, respectively (P < 0.05-0.001). Similarly, the activities of duodenal maltase, sucrase, lactase, glutamyl transpeptidase, and dipeptidyl-peptidase IV (215 +/- 28% of controls; P < 0.001) were increased by GLP-2. Oral or duodenal administration of glucose or maltose did not reveal any differences in the ability of GLP-2-treated mice to absorb these nutrients, possibly because of decreases in expression of the glucose transporters sodium-dependent glucose transporter-1 (SGLT-1) and GLUT-2. In contrast, absorption of leucine plus triolein was increased after duodenal administration in GLP-2-treated mice (P < 0.01-0.001). Finally, GLP-2 did not alter other markers of intestinal or pancreatic gene expression, including levels of mRNA transcripts for ornithine decarboxylase, multidrug resistance gene, amylase, proglucagon, proinsulin, and prosomatostatin. Thus induction of intestinal growth by GLP-2 in wild-type mice results in a normal-to-increased capacity for nutrient digestion and absorption in vivo.
Brubaker
P L
PL
Department of Physiology, University of Toronto, Ontario, Canada.
Izzo
A
A
Hill
M
M
Drucker
D J
DJ
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000502:physiology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects / Q000502:physiology; D005260:Female; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000494:pharmacology; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007421:Intestine, Small / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D043322:Lactase; D008320:Maltose / Q000494:pharmacology; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D013393:Sucrase / Q000378:metabolism; D000520:alpha-Glucosidases / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D005768:Gastrointestinal Hormones; D053767:Glucagon-Like Peptide 2; D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins; D010455:Peptides; C495678:Slc2a1 protein, mouse; D004763:Glucagon-Like Peptides; D008320:Maltose; D005723:gamma-Glutamyltransferase; D043322:Lactase; D000520:alpha-Glucosidases; D001616:beta-Galactosidase; D013393:Sucrase; D018819:Dipeptidyl Peptidase 4; D005947:Glucose