Laboratorio di Fisiologia Generale, Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari (STEMBIO), Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy.
J Endocrinol. 2012 Jun;213(3):277-84. doi: 10.1530/JOE-12-0092. Epub 2012 Mar 28.
We investigated the potential anorectic action of peripherally administered glucagon-like peptide 2 (GLP2) in lean and diet-induced obese (DIO) mice. Mice, fasted for 16 h, were injected i.p. with native GLP2 or [Gly2]GLP2, stable analog of GLP2, before or after GLP2 (3-33), a GLP2 receptor (GLP2R) antagonist, or exendin (9-39), a GLP1R antagonist. Food intake was measured at intervals 1, 2, 4, 8, and 24 h postinjection. In addition, we tested in lean mice the influence of [Gly2]GLP2 on gastric emptying and the effects of GLP1 alone or in combination with [Gly2]GLP2 on food intake. [Gly2]GLP2 dose dependently and significantly inhibited food intake in lean and DIO mice. The reduction of food intake occurred in the first hour postinjection and it was sustained until 4 h postinjection in lean mice while it was sustained until 2 h postinjection in DIO mice. GLP2 significantly inhibited food intake in both lean and DIO mice but only in the first hour postinjection. The efficiency of [Gly2]GLP2 or GLP2 in suppressing food intake was significantly weaker in DIO mice compared with lean animals. The [Gly2]GLP2 anorectic actions were blocked by the GLP2R antagonist GLP2 (3-33) or by the GLP1R antagonist exendin (9-39). The coadministration of [Gly2]GLP2 and GLP1 did not cause additive effects. [Gly2]GLP2 decreased the gastric emptying rate. Results suggest that GLP2 can reduce food intake in mice in the short term, likely acting at a peripheral level. DIO mice are less sensitive to the anorectic effect of the peptide.
我们研究了外周给予胰高血糖素样肽 2（GLP2）在瘦鼠和饮食诱导肥胖（DIO）鼠中的潜在抑制食欲作用。禁食 16 小时的小鼠，在注射 GLP2 受体（GLP2R）拮抗剂 GLP2（3-33）或 GLP1R 拮抗剂 exendin（9-39）前后，通过腹腔内注射给予内源性 GLP2 或 GLP2 的稳定类似物 [Gly2]GLP2。在注射后 1、2、4、8 和 24 小时测量食物摄入量。此外，我们在瘦鼠中测试了 [Gly2]GLP2 对胃排空的影响，以及单独给予 GLP1 或与 [Gly2]GLP2 联合给予 GLP1 对食物摄入的影响。[Gly2]GLP2 剂量依赖性地显著抑制瘦鼠和 DIO 鼠的食物摄入。在注射后 1 小时内，这种抑制作用明显，在瘦鼠中持续到 4 小时，而在 DIO 鼠中持续到 2 小时。GLP2 显著抑制了瘦鼠和 DIO 鼠的食物摄入，但仅在注射后 1 小时内。与瘦鼠相比，[Gly2]GLP2 或 GLP2 抑制食物摄入的效率在 DIO 鼠中明显较弱。[Gly2]GLP2 的厌食作用被 GLP2R 拮抗剂 GLP2（3-33）或 GLP1R 拮抗剂 exendin（9-39）阻断。[Gly2]GLP2 和 GLP1 的共同给药没有引起相加作用。[Gly2]GLP2 降低了胃排空率。结果表明，GLP2 可以在短期内减少小鼠的食物摄入，可能在外周水平发挥作用。DIO 鼠对肽的厌食作用不敏感。
