Maki L W, Keizer J
Institute of Theoretical Dynamics, University of California, Davis 95616.
Am J Physiol. 1995 Mar;268(3 Pt 1):C780-91. doi: 10.1152/ajpcell.1995.268.3.C780.
We explore possible kinetic mechanisms responsible for the oscillatory (pulsatile) secretion of insulin observed in vitro when pancreatic islets or islet-derived cells are perifused with glucose. Three primary processes are included: 1) glucose stimulation of insulin secretion, controlled by glucokinase; 2) uptake of glucose through GLUT transporters; and 3) glucose metabolism. Perifusion is approximated as a limiting case of a chemical flow reactor. Using experimentally determined rate laws for the three processes, we examine the effects of exogenous insulin as a phenomenological activator and inhibitor of secretion. The resulting differential equations support oscillations using either direct or indirect inhibition by insulin. The oscillations have many of the characteristics observed in vitro, although the indirect model is in better overall agreement with experiment. We conclude that the mechanisms explored here may help explain insulin oscillations for HIT cells, but not for islets, and predict that oscillations can be modulated by including insulin in the perifusion medium.
我们探究了可能导致体外观察到的胰岛素振荡（脉冲式）分泌的动力学机制，当胰岛或胰岛衍生细胞用葡萄糖进行灌流时会出现这种现象。其中包括三个主要过程：1）由葡萄糖激酶控制的葡萄糖对胰岛素分泌的刺激；2）通过葡萄糖转运蛋白（GLUT）摄取葡萄糖；3）葡萄糖代谢。灌流可近似看作化学流动反应器的一种极限情况。利用实验确定的这三个过程的速率定律，我们研究了外源性胰岛素作为分泌的唯象激活剂和抑制剂的作用。所得的微分方程支持胰岛素通过直接或间接抑制产生振荡。这些振荡具有许多体外观察到的特征，尽管间接模型总体上与实验结果更相符。我们得出结论，这里探究的机制可能有助于解释人胰岛素瘤细胞（HIT细胞）的胰岛素振荡，但不适用于胰岛，并预测通过在灌流培养基中加入胰岛素可以调节振荡。
