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

TY - JOUR

T1 - Insulin-like growth factor I and glucagon-like peptide-2 responses to fasting followed by controlled or ad libitum refeeding in rats

AU - Nelson, David W

AU - Murali, Sangita G

AU - Liu, Xiaowen

AU - Koopmann, Matthew C

AU - Holst, Jens Juul

AU - Ney, Denise M

PY - 2008/4

Y1 - 2008/4

N2 - 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.

AB - 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.

KW - Adaptation, Physiological

KW - Animals

KW - Body Weight

KW - Dose-Response Relationship, Drug

KW - Eating

KW - Fasting

KW - Glucagon-Like Peptide 2

KW - Ileum

KW - Infusions, Intravenous

KW - Insulin

KW - Insulin-Like Growth Factor Binding Protein 3

KW - Insulin-Like Growth Factor Binding Protein 5

KW - Insulin-Like Growth Factor I

KW - Intestinal Mucosa

KW - Intubation, Gastrointestinal

KW - Jejunum

KW - Male

KW - Nitrogen

KW - Parenteral Nutrition

KW - Peptide Fragments

KW - Proglucagon

KW - RNA, Messenger

KW - Rats

KW - Rats, Sprague-Dawley

KW - Regeneration

KW - Sodium-Glucose Transporter 1

KW - Sucrase

KW - Time Factors

U2 - 10.1152/ajpregu.00238.2007

DO - 10.1152/ajpregu.00238.2007

M3 - Journal article

C2 - 18256135

SN - 0363-6119

VL - 294

SP - R1175-84

JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology

JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology

IS - 4

ER -