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

David W. Nelson, Sangita G. Murali, Xiaowen Liu, Matthew Koopman, Jens J. Holst, Denise M. Ney

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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-23-33) 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 (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume294
Issue number4
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

Fingerprint

Glucagon-Like Peptide 2
Insulin-Like Growth Factor I
Fasting
Messenger RNA
Regeneration
Sodium-Glucose Transporter 1
Growth
Proglucagon
Sucrase
Food
Intestines
Body Weight

Keywords

  • GLP-2
  • Parenteral nutrition
  • Proglucagon
  • Sodium-glucose linked transporter-1

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Insulin-like growth factor I and glucagon-like peptide-2 responses to fasting followed by controlled or ad libitum refeeding in rats. / Nelson, David W.; Murali, Sangita G.; Liu, Xiaowen; Koopman, Matthew; Holst, Jens J.; Ney, Denise M.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 294, No. 4, 01.04.2008.

Research output: Contribution to journalArticle

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