Insulin-like growth factor I and glucagon-like peptide-2 responses to fasting followed by controlled or ad libitum refeeding in rats.
Luminal nutrients stimulate structural and functional regeneration in the intestine through mechanisms thought to involve insulin-like growth factor I (IGF-I) and glucagon-like peptide-2 (GLP-2). We investigated the relationship between IGF-I and GLP-2 responses and mucosal growth in rats fasted for 48 h and then refed for 2 or 4 days by continuous intravenous or intragastric infusion or ad libitum feeding. Fasting induced significant decreases in body weight, plasma concentrations of IGF-I and bioactive GLP-2, jejunal mucosal cellularity (mass, protein, DNA, and villus height), IGF-I mRNA, and ileal proglucagon mRNA. Plasma IGF-I concentration was restored to fed levels with 2 days of ad libitum refeeding but not with 4 days of intravenous or intragastric refeeding. Administration of an inhibitor of endogenous GLP-2 (rat GLP-2 3-33) during ad libitum refeeding partially attenuated mucosal growth and prevented the increase in plasma IGF-I to fed levels; however, plasma GLP-2 and jejunal IGF-I mRNA were restored to fed levels. Intragastric refeeding restored intestinal cellularity and functional capacity (sucrase activity and sodium-glucose transporter-1 expression) to fed levels, whereas intravenous refeeding had no effect. Intestinal regeneration after 4 days of intragastric or 2 days of ad libitum refeeding was positively associated with increases in plasma concentrations of GLP-2 and jejunal IGF-I mRNA. These data suggest that luminal nutrients stimulate intestinal growth, in part, by increased expression of both GLP-2 and IGF-I.
Nelson
David W
DW
Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Murali
Sangita G
SG
Liu
Xiaowen
X
Koopmann
Matthew C
MC
Holst
Jens J
JJ
Ney
Denise M
DM
D000222:Adaptation, Physiological; D000818:Animals; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004435:Eating; D005215:Fasting / Q000097:blood*; D053767:Glucagon-Like Peptide 2 / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000254:growth & development / Q000378:metabolism; D007441:Intubation, Gastrointestinal; D007583:Jejunum / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D009584:Nitrogen / Q000378:metabolism; D010288:Parenteral Nutrition; D010446:Peptide Fragments / Q000494:pharmacology; D052336:Proglucagon / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism; D013393:Sucrase / Q000378:metabolism; D013997:Time Factors
D053767:Glucagon-Like Peptide 2; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D010446:Peptide Fragments; D012333:RNA, Messenger; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; C451520:glucagon-like peptide-2 (3-33); D052336:Proglucagon; D007334:Insulin-Like Growth Factor I; D013393:Sucrase; D009584:Nitrogen