Nunemaker Craig S, Wasserman David H, McGuinness Owen P, Sweet Ian R, Teague Jeanette C, Satin Leslie S
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Am J Physiol Endocrinol Metab. 2006 Mar;290(3):E523-9. doi: 10.1152/ajpendo.00392.2005. Epub 2005 Oct 25.
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 approximately 5 to approximately 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 ( approximately 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.
大多数物种的胰岛对葡萄糖升高的反应是双相胰岛素分泌，其特征是有一个急剧的第一相峰值和一个缓慢上升的第二相。然而，体外培养的小鼠胰岛缺乏强劲的第二相。迄今为止，这一观察结果尚未在体内得到进一步验证。因此，我们比较了清醒小鼠与体外分离的小鼠胰岛的胰岛素分泌情况。在清醒小鼠的颈动脉和颈静脉导管手术植入1周后，测量其对高血糖钳夹的动脉血浆胰岛素反应。使用夹子将供体小鼠的血液输给小鼠以维持血容量，从而能够频繁进行动脉采样。当体内血浆葡萄糖从约5 mM升高至约13 mM时，胰岛素升至高于基础分泌403±73%的第一相峰值（n = 5），随后是平均为289±41%的上升第二相。相比之下，经灌注的小鼠胰岛（每次试验约75个胰岛）第一相反应相似，为508±94%（n = 4），但第二相较小且几乎平稳，为169±9%（n = 4，P<0.05）。此外，第二相反应的斜率在小鼠中显著不同于零（2.63±0.39%/分钟，P<0.01），而经灌注的胰岛则相反（0.18±0.14%/分钟，P>0.30）。小鼠的胰岛素浓度也呈现出脉动模式（周期：4.2±0.4分钟，n = 8）。因此，清醒小鼠对葡萄糖升高的反应是双相和脉动性胰岛素分泌，与其他物种一样。在体内观察到的强劲第二相表明，产生第二相胰岛素分泌所需的过程可能因胰岛分离而被消除。
