Sangild Per T, Malo Christiane, Schmidt Mette, Petersen Yvette M, Elnif Jan, Holst Jens J, Buddington Randal K
Department of Human Nutrition, University of Copenhagen, Frederiksberg, Denmark.
Am J Physiol Regul Integr Comp Physiol. 2007 Dec;293(6):R2179-84. doi: 10.1152/ajpregu.00395.2007. Epub 2007 Sep 26.
Exogenous glucagon-like peptide 2 (GLP-2) prevents intestinal atrophy and increases nutrient absorption in term newborn pigs receiving total parenteral nutrition (TPN). We tested the hypothesis that the immature intestine of fetuses and preterm neonates has a diminished nutrient absorption response to exogenous GLP-2. This was accomplished using catheterized fetal pigs infused for 6 days (87-91% of gestation) with GLP-2 (25 nmol.kg(-1).day(-1) iv; n = 7) or saline (n = 7), and cesarean-delivered preterm pigs (92% of gestation) that received TPN with GLP-2 (25 nmol.kg(-1).day(-1) iv; n = 8) or saline (n = 7) for 6 days after birth. Responses to GLP-2 were assessed by measuring intestinal dimensions, absorption of nutrients (glucose, leucine, lysine, proline) by intact tissues and brush border membrane vesicles, and abundance of sodium-glucose cotransporter mRNA. Infusion of GLP-2 increased circulating GLP-2 levels in fetuses, but did not increase intestinal mass or absorption of nutrients by intact tissues and brush border membrane vesicles, except for lysine. Administration of exogenous GLP-2 to preterm TPN-fed pigs similarly did not increase rates of nutrient absorption, yet nutrient absorption capacities of the entire small intestine tended to increase (+10-20%, P < 0.10) compared with TPN alone due to increased intestinal mass (+30%, P < 0.05). GLP-2 infusion did not increase sodium-glucose cotransporter-1 mRNA abundance in fetuses or postnatal preterm pigs. Hence, the efficacy of exogenous GLP-2 to improve nutrient absorption by the intestine of fetal and preterm pigs is limited compared with term pigs and more mature animals and humans.
外源性胰高血糖素样肽2（GLP-2）可预防足月新生仔猪接受全胃肠外营养（TPN）时的肠道萎缩并增加营养吸收。我们检验了以下假设：胎儿和早产新生儿未成熟的肠道对外源性GLP-2的营养吸收反应减弱。这是通过对妊娠87 - 91%的胎儿猪进行插管，静脉输注GLP-2（25 nmol·kg⁻¹·d⁻¹；n = 7）或生理盐水（n = 7），持续6天来实现的；对于剖宫产的早产猪（妊娠92%），在出生后6天接受含GLP-2（25 nmol·kg⁻¹·d⁻¹；n = 8）或生理盐水（n = 7）的TPN。通过测量肠道尺寸、完整组织和刷状缘膜囊泡对营养物质（葡萄糖、亮氨酸、赖氨酸、脯氨酸）的吸收以及钠-葡萄糖共转运蛋白mRNA丰度来评估对GLP-2的反应。输注GLP-2可提高胎儿体内循环GLP-2水平，但除赖氨酸外，未增加完整组织和刷状缘膜囊泡的肠道质量或营养物质吸收。对接受TPN的早产猪给予外源性GLP-2同样未提高营养物质吸收速率，但与仅接受TPN相比，由于肠道质量增加（+30%，P < 0.05），整个小肠的营养物质吸收能力有增加的趋势（+10 - 20%，P < 0.10）。GLP-2输注未增加胎儿或出生后早产猪中钠-葡萄糖共转运蛋白-1 mRNA丰度。因此，与足月猪以及更成熟的动物和人类相比，外源性GLP-2改善胎儿和早产猪肠道营养吸收的功效有限。
