Insulin-like growth factor I and glucagon-like peptide-2 responses to fasting followed by controlled or ad libitum refeeding in rats

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David W Nelson, Sangita G Murali, Xiaowen Liu, Matthew C Koopmann, Jens Juul Holst, Denise M Ney

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.

Original languageEnglish
JournalAmerican Journal of Physiology: Regulatory, Integrative and Comparative Physiology
Issue number4
Pages (from-to)R1175-84
Publication statusPublished - Apr 2008

    Research areas

  • Adaptation, Physiological, Animals, Body Weight, Dose-Response Relationship, Drug, Eating, Fasting, Glucagon-Like Peptide 2, Ileum, Infusions, Intravenous, Insulin, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor Binding Protein 5, Insulin-Like Growth Factor I, Intestinal Mucosa, Intubation, Gastrointestinal, Jejunum, Male, Nitrogen, Parenteral Nutrition, Peptide Fragments, Proglucagon, RNA, Messenger, Rats, Rats, Sprague-Dawley, Regeneration, Sodium-Glucose Transporter 1, Sucrase, Time Factors

ID: 132049370