Insulin-independent effects of GLP-1 on canine liver glucose metabolism: duration of infusion and involvement of hepatoportal region
Insulin-independent effects of GLP-1 on canine liver glucose metabolism: duration of infusion and involvement of hepatoportal region
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DOI：
10.1152/ajpendo.00035.2004
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发表时间：
2004-07-01
影响因子：
5.1
通讯作者：
Cherrington, AD
中科院分区：
文献类型：
--
作者：
Dardevet, D;Moore, MC;Cherrington, AD
通过使用示踪剂和动静脉差异技术，在清醒的狗中评估胰高血糖素样肽-1 (GLP-1) 对体内葡萄糖处理是否具有胰岛素依赖性作用。基础期后，每个实验由三个时期（P1、P2、P3）组成，在此期间输注生长抑素、胰高血糖素、胰岛素和葡萄糖。对照组 (C) 在 P1、P2 和 P3 中接受生理盐水，PePe 组在 P1 中接受生理盐水，在 P2 和 P3 中接受外周 GLP-1 (7.5 pmol.kg(-1).min(-1)) (Pe; iv)，PePo 组在 P1 中接受生理盐水，在外周 (iv) (P2) 中接受 GLP-1 (7.5 pmol.kg(-1).min(-1))，然后进入门静脉 (Po; P3)。葡萄糖和胰岛素浓度分别增加至基础值的两倍和四倍，而胰高血糖素仍保持基础值。在 P2 期间（类似于 200 pM），PePe 和 PePo 组的 GLP-1 水平增加相似，而在 P3 期间，PePo 与 PePe 组的门静脉 GLP-1 水平显着增加（3 倍）。在所有组中，净肝葡萄糖摄取（NHGU）发生在 P1 期间。在 P2 期间，所有组中 NHGU 略有增加，但不显着。 P3期间，PePe和PePo组的NHGU增加程度比C组更大，但GLP-1输注途径没有显示出显着影响（分别为16.61+/-2.91和14.67+/-2.09 vs. 4.22+/-1.57 mumol.kg(-1).min(-1)）。结论：GLP-1 增加肝脏中的葡萄糖处理，与胰岛素分泌无关；其完全发挥作用需要长期输注。输注途径不会改变肝脏反应。
Whether glucagon-like peptide-1 (GLP-1) has insulin-independent effects on glucose disposal in vivo was assessed in conscious dogs by use of tracer and arteriovenous difference techniques. After a basal period, each experiment consisted of three periods (P1, P2, P3) during which somatostatin, glucagon, insulin, and glucose were infused. The control group (C) received saline in P1, P2, and P3, the PePe group received saline in P1 and GLP-1 (7.5 pmol.kg(-1).min(-1)) peripherally (Pe; iv) in P2 and P3, and the PePo group received saline in P1 and GLP-1 peripherally (iv) (P2) and then into the portal vein (Po; P3). Glucose and insulin concentrations increased to two- and fourfold basal, respectively, and glucagon remained basal. GLP-1 levels increased similarly in the PePe and PePo groups during P2 (similar to200 pM), whereas portal GLP-1 levels were significantly increased (3-fold) in PePo vs. PePe during P3. In all groups, net hepatic glucose uptake (NHGU) occurred during P1. During P2, NHGU increased slightly but not significantly in all groups. During P3, NHGU increased in PePe and PePo groups to a greater extent than in C, but no significant effect of the route of infusion of GLP-1 was demonstrated (16.61+/-2.91 and 14.67+/-2.09 vs. 4.22+/-1.57 mumol.kg(-1).min(-1), respectively). In conclusion: GLP-1 increased glucose disposal in the liver independently of insulin secretion; its full action required long-term infusion. The route of infusion did not modify the hepatic response.