Enteral nutrients potentiate the intestinotrophic action of glucagon-like peptide-2 in association with increased insulin-like growth factor-I responses in rats.

Abstract

Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, intestinotrophic hormone derived from posttranslational processing of proglucagon in the distal bowel. GLP-2 is thought to act through indirect mediators, such as IGF-I. We investigated whether intestinal expression of GLP-2 and IGF-I system components are increased with the mucosal growth induced by enteral nutrient (EN) and/or a low dose of GLP-2 in parenterally fed rats. Rats were randomized to four treatment groups using a 2 x 2 design and maintained with parenteral nutrition (PN) for 7 days: PN alone, EN, GLP-2, and EN+GLP-2; n = 7-9. The two main treatment effects are +/-GLP-2 (100 microg.kg body wt(-1).day(-1)) and +/-EN (43% of energy needs, days 4-6). Combination treatment with EN+GLP-2 induced synergistic intestinal growth in ileum, resulting in greater mucosal cellularity, sucrase segmental activity, and gain of body weight (ENxGLP-2, P < 0.04). In addition, EN+GLP-2 induced a significant 28% increase in plasma concentration of bioactive GLP-2, a significant 102% increase in ileal proglucagon mRNA with no change in ileal dipeptidyl peptidase-IV (DPP-IV) specific activity, and significantly reduced plasma DPP-IV activity compared with GLP-2. This indicates that EN potentiates the intestinotrophic action of GLP-2. Proliferation of enterocytes due to GLP-2 infusion was associated with greater expression of ileal proglucagon, GLP-2 receptor, IGF-I, IGF binding protein-3 mRNAs, and greater IGF-I peptide concentration in ileum (P < 0.032). Ileal IGF-I mRNA was positively correlated with expression of proglucagon, GLP-2R, and IGFBP-5 mRNAs (R2 = 0.43-0.56, P < 0.0001). Our findings support the hypothesis that IGF-I is one of the downstream mediators of GLP-2 action in a physiological model of intestinal growth.

• Authors: Xiaowen Liu, Sangita G Murali, Jens J Holst, Denise M Ney
• Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 295 Issue 6 Pg. R1794-802 (Dec 2008) ISSN: 0363-6119 [Print] United States
• PMID: 18832087 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Glucagon-Like Peptide 2
• Glucagon-Like Peptide-2 Receptor
• Insulin-Like Growth Factor Binding Protein 3
• Insulin-Like Growth Factor Binding Protein 5
• RNA, Messenger
• Receptors, Glucagon
• Recombinant Proteins
• Proglucagon
• Insulin-Like Growth Factor I
• Sucrase
• Dipeptidyl Peptidase 4
• Nitrogen

Topics

• Animals
• Body Weight
• Cell Proliferation
• Dipeptidyl Peptidase 4 (metabolism)
• Enteral Nutrition
• Enterocytes (metabolism)
• Glucagon-Like Peptide 2 (administration & dosage, metabolism)
• Glucagon-Like Peptide-2 Receptor
• Humans
• Ileum (growth & development, metabolism)
• Infusions, Intravenous
• Insulin-Like Growth Factor Binding Protein 3 (metabolism)
• Insulin-Like Growth Factor Binding Protein 5 (metabolism)
• Insulin-Like Growth Factor I (genetics, metabolism)
• Intestinal Mucosa (metabolism)
• Intestines (enzymology, growth & development)
• Jejunum (growth & development, metabolism)
• Male
• Nitrogen (metabolism)
• Parenteral Nutrition
• Proglucagon (metabolism)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Glucagon (metabolism)
• Recombinant Proteins (metabolism)
• Signal Transduction
• Sucrase (metabolism)
• Time Factors
• Up-Regulation