Naimi R M, Madsen K B, Askov-Hansen C, Brandt C F, Hartmann B, Holst J J, Mortensen P B, Jeppesen P B
Department of Gastroenterology CA-2121, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Regul Pept. 2013 Jun 10;184:47-53. doi: 10.1016/j.regpep.2013.03.023. Epub 2013 Mar 15.
Glucagon-like peptide 2 (GLP-2), secreted endogenously from L-cells in the distal bowel in relation to meals, modulates intestinal absorption by adjusting gastric emptying and secretion and intestinal growth. Short bowel syndrome (SBS) patients with distal intestinal resections have attenuated endogenous GLP-2 secretion, which may contribute to their rapid gastric emptying, gastric hypersecretion and poor intestinal adaptation, whereas SBS patients with preserved terminal ileum and colon, who have a constantly elevated GLP-2 secretion, seem to do better in these respects. This study compared effects of continuous, subcutaneous (s.c.), exogenous GLP-2 infusion (CONT-GLP-2) versus three daily s.c. GLP-2 injections (TID-GLP-2) on intestinal absorption in SBS patients.
Eight SBS patients (5 F, 3 M; 60±7 years; remnant small bowel 111±62 cm; 1 with 50% colon) were studied. In an open-label, sequential study, the 72-hour baseline admission was followed by two dose-equivalent, 21-day, dosing regimens; CONT-GLP-2, providing 1.0mg/day by a MiniMed insulin pump and TID-GLP-2, providing 0.33 mg injections in relation to three meals, separated by a washout period of at least 3 weeks. During admissions, the intestinal absorption was evaluated by analysing a double portion of the diet, faecal and urinary excretions. Post-absorptive plasma citrulline, reflecting enterocyte mass, was measured by HPLC.
Compared to baseline, both GLP-2 dosing regimens reduced diarrhoea (CONT-GLP-2: 749±815 g/d and TID-GLP-2: 877±1004 g/d, p=0.01) and increased wet weight absorption (CONT-GLP-2: 19±19% and TID-GLP-2: 25±21%, p=0.003). Significant increases in plasma citrulline (CONT-GLP-2: 7.5±7 μmol/L and TID-GLP-2, 12.7±8 μmol/L; p=0.001) suggesting intestinotrophic effects in relation to GLP-2 treatment, are followed by increases in relative absorption of energy, carbohydrate and fat. No significant difference was seen on any of the absorptive parameters measured between the two dosing regimens.
Both GLP-2 regimens significantly reduced diarrhoea in SBS patients, but a significant difference between continuous GLP-2 administration and TID injections could not be detected in a study of this size.
胰高血糖素样肽2（GLP - 2）由远端肠道的L细胞根据进餐情况内源性分泌，通过调节胃排空、分泌及肠道生长来调控肠道吸收。行远端肠切除的短肠综合征（SBS）患者内源性GLP - 2分泌减弱，这可能导致其胃排空过快、胃酸分泌过多及肠道适应性差，而保留回肠末端和结肠且GLP - 2分泌持续升高的SBS患者在这些方面似乎表现较好。本研究比较了持续皮下（s.c.）外源性输注GLP - 2（CONT - GLP - 2）与每日三次皮下注射GLP - 2（TID - GLP - 2）对SBS患者肠道吸收的影响。
对8例SBS患者（5例女性，3例男性；年龄60±7岁；残余小肠111±62 cm；1例保留50%结肠）进行研究。在一项开放标签的序贯研究中，72小时基线期后是两个等效剂量、为期21天的给药方案；CONT - GLP - 2通过美敦力胰岛素泵每日提供1.0mg，TID - GLP - 2在三餐时各注射0.33mg，中间间隔至少3周的洗脱期。住院期间，通过分析双倍量饮食、粪便及尿液排泄物评估肠道吸收情况。采用高效液相色谱法测定反映肠细胞量的吸收后血浆瓜氨酸水平。
与基线相比，两种GLP - 2给药方案均减少了腹泻（CONT - GLP - 2：749±815g/天，TID - GLP - 2：877±1004g/天，p = 0.01），并增加了湿重吸收（CONT - GLP - 2：19±19%，TID - GLP - 2：25±21%，p = 0.003）。血浆瓜氨酸显著升高（CONT - GLP - 2：7.5±7μmol/L，TID - GLP - 2：12.7±8μmol/L；p = 0.001），提示GLP - 2治疗具有肠营养作用，随后能量、碳水化合物及脂肪的相对吸收增加。两种给药方案之间在任何测量的吸收参数上均未观察到显著差异。
两种GLP - 2方案均显著减少了SBS患者的腹泻，但在本规模的研究中未检测到持续输注GLP - 2与每日三次注射之间的显著差异。
