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Enteral nutrients potentiate the intestinotrophic action of glucagon-like peptide-2 in association with increased insulin-like growth factor-I responses in rats.
Am J Physiol Regul Integr Comp Physiol. 2008 Dec; 295(6):R1794-802.AJ

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.

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Authors+Show Affiliations

Liu X
Department of Nutritional Sciences, University of Wisconsin-Madison, 1415 Linden Drive, Madison, WI 53706, USA.
Murali SG
No affiliation info available
Holst JJ
No affiliation info available
Ney DM
No affiliation info available

MeSH

AnimalsBody WeightCell ProliferationDipeptidyl Peptidase 4Enteral NutritionEnterocytesGlucagon-Like Peptide 2Glucagon-Like Peptide-2 ReceptorHumansIleumInfusions, IntravenousInsulin-Like Growth Factor Binding Protein 3Insulin-Like Growth Factor Binding Protein 5Insulin-Like Growth Factor IIntestinal MucosaIntestinesJejunumMaleNitrogenParenteral NutritionProglucagonRNA, MessengerRatsRats, Sprague-DawleyReceptors, GlucagonRecombinant ProteinsSignal TransductionSucraseTime FactorsUp-Regulation

Pub Type(s)

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.

Language

eng

PubMed ID

18832087

Citation

Liu, Xiaowen, et al. "Enteral Nutrients Potentiate the Intestinotrophic Action of Glucagon-like Peptide-2 in Association With Increased Insulin-like Growth factor-I Responses in Rats." American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 295, no. 6, 2008, pp. R1794-802.
Liu X, Murali SG, Holst JJ, et al. Enteral nutrients potentiate the intestinotrophic action of glucagon-like peptide-2 in association with increased insulin-like growth factor-I responses in rats. Am J Physiol Regul Integr Comp Physiol. 2008;295(6):R1794-802.
Liu, X., Murali, S. G., Holst, J. J., & Ney, D. M. (2008). Enteral nutrients potentiate the intestinotrophic action of glucagon-like peptide-2 in association with increased insulin-like growth factor-I responses in rats. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 295(6), R1794-802. https://doi.org/10.1152/ajpregu.90616.2008
Liu X, et al. Enteral Nutrients Potentiate the Intestinotrophic Action of Glucagon-like Peptide-2 in Association With Increased Insulin-like Growth factor-I Responses in Rats. Am J Physiol Regul Integr Comp Physiol. 2008;295(6):R1794-802. PubMed PMID: 18832087.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enteral nutrients potentiate the intestinotrophic action of glucagon-like peptide-2 in association with increased insulin-like growth factor-I responses in rats. AU - Liu,Xiaowen, AU - Murali,Sangita G, AU - Holst,Jens J, AU - Ney,Denise M, Y1 - 2008/10/01/ PY - 2008/10/4/pubmed PY - 2009/1/23/medline PY - 2008/10/4/entrez SP - R1794 EP - 802 JF - American journal of physiology. Regulatory, integrative and comparative physiology JO - Am J Physiol Regul Integr Comp Physiol VL - 295 IS - 6 N2 - 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. SN - 0363-6119 UR - https://www.unboundmedicine.com/medline/citation/18832087/Enteral_nutrients_potentiate_the_intestinotrophic_action_of_glucagon_like_peptide_2_in_association_with_increased_insulin_like_growth_factor_I_responses_in_rats_ L2 - https://journals.physiology.org/doi/10.1152/ajpregu.90616.2008?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -