Insulin secretion in the conscious mouse is biphasic and pulsatile
Insulin secretion in the conscious mouse is biphasic and pulsatile
复制标题
DOI：
10.1152/ajpendo.00392.2005
复制
发表时间：
2006-03-01
影响因子：
5.1
通讯作者：
Satin, LS
中科院分区：
文献类型：
--
作者：
Nunemaker, CS;Wasserman, DH;Satin, LS
大多数物种中的胰岛以双相胰岛素分泌对葡萄糖增加作出反应，其特征在于尖锐的第一相峰和缓慢上升的第二相。然而，体外小鼠胰岛缺乏稳健的第二相。迄今为止，该观察结果尚未在体内扩展。因此，我们比较了清醒小鼠与离体小鼠胰岛的胰岛素分泌。在清醒小鼠中，在颈动脉和颈静脉导管手术植入后1周，测量动脉血浆胰岛素对高血糖钳夹的反应。使用夹子将来自供体小鼠的血液输注小鼠以维持血容量，允许频繁的动脉取样。当体内血浆葡萄糖从接近5 mM升高至接近13 mM时，胰岛素升高至高于基础分泌403 +/- 73%的第一阶段峰值（n = 5），随后是平均289 +/-41%的第二阶段升高。相比之下，灌流的小鼠胰岛（类似于75个胰岛/试验）以508 +/-94%（n = 4）的类似的第一阶段响应，但169 +/-9%（n = 4，P < 0.05）的较小且几乎平坦的第二阶段响应。此外，第二阶段反应的斜率在小鼠中与零显著不同（2.63 +/-0.39%/ min，P < 0.01），与灌流胰岛（0.18 +/-0.14%/ min，P > 0.30）形成对比。小鼠还显示胰岛素浓度的脉动模式（周期：4.2 +/-0.4分钟，n = 8）。因此，清醒的小鼠对葡萄糖增加的反应是双相和脉冲式胰岛素分泌，与其他物种一样。在体内观察到的稳健的第二相表明，产生第二相胰岛素分泌所需的过程可以通过胰岛分离来消除。
Islets in most species respond to increased glucose with biphasic insulin secretion, marked by a sharp first- phase peak and a slowly rising second phase. Mouse islets in vitro, however, lack a robust second phase. To date, this observation has not been extended in vivo. We thus compared insulin secretion from conscious mice with isolated mouse islets in vitro. The arterial plasma insulin response to a hyperglycemic clamp was measured in conscious mice 1 wk after surgical implantation of carotid artery and jugular vein catheters. Mice were transfused using clamps with blood from a donor mouse to maintain blood volume, allowing frequent arterial sampling. When plasma glucose in vivo was raised from similar to 5 to similar to 13 mM, insulin rose to a first-phase peak of 403 +/- 73% above basal secretion (n = 5), followed by a rising second phase of mean 289 +/- 41%. In contrast, perifused mouse islets (similar to 75 islets/ trial) responded with a similar first phase of 508 +/- 94% (n = 4) but a smaller and virtually flat second phase of 169 +/- 9% (n = 4, P < 0.05). Furthermore, the slope of the second-phase response differed significantly from zero in mice (2.63 +/- 0.39%/ min, P < 0.01), in contrast to perifused islets (0.18 +/- 0.14%/ min, P > 0.30). Mice also displayed pulsatile patterns in insulin concentration ( period: 4.2 +/- 0.4 min, n = 8). Conscious mice thus responded to increased glucose with biphasic and pulsatile insulin secretion, as in other species. The robust second phase observed in vivo suggests that the processes needed to generate second-phase insulin secretion may be abrogated by islet isolation.