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 Juul
AU - Ney, Denise M
PY - 2008
Y1 - 2008
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 insulin-like growth factor I (IGF-I). We investigated if 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 parentally-fed rats. Rats were randomized to 4 treatment groups using a 2x2 design and maintained with parental nutrition (PN) for 7 days: PN alone, EN, GLP-2, EN+GLP-2, n=7-9. The 2 main treatment effects are: +/-GLP-2 (100 microg/kg body wt/day) and +/-EN (43% of energy needs, day4-6). 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 to 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 (R(2)=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. Key words: parenteral nutrition, GLP-2 receptor, IGF binding protein-3 and -5, proglucagon.
AB - 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 insulin-like growth factor I (IGF-I). We investigated if 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 parentally-fed rats. Rats were randomized to 4 treatment groups using a 2x2 design and maintained with parental nutrition (PN) for 7 days: PN alone, EN, GLP-2, EN+GLP-2, n=7-9. The 2 main treatment effects are: +/-GLP-2 (100 microg/kg body wt/day) and +/-EN (43% of energy needs, day4-6). 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 to 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 (R(2)=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. Key words: parenteral nutrition, GLP-2 receptor, IGF binding protein-3 and -5, proglucagon.
U2 - 10.1152/ajpregu.90616.2008
DO - 10.1152/ajpregu.90616.2008
M3 - Journal article
C2 - 18832087
SN - 0363-6119
SP - 295:R1794-1802
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
ER -