Borg M A, Sherwin R S, Borg W P, Tamborlane W V, Shulman G I
Yale University School of Medicine, Department of Internal Medicine, New Haven, Connecticut 06520, USA.
J Clin Invest. 1997 Jan 15;99(2):361-5. doi: 10.1172/JCI119165.
The ventromedial hypothalamic nucleus (VMH) is necessary for the integrated hormonal response to hypoglycemia. To determine the role of the VMH as a glucose sensor, we performed experiments designed to specifically prevent glucopenia in the VMH, while producing hypoglycemia elsewhere. We used awake chronically catheterized rats, in which local VMH glucose perfusion (100 mM or 15 mM of D-glucose) was combined with a sequential euglycemic-hypoglycemic clamp. In two control groups the VMH was perfused either with (a) an iso-osmotic solution lacking glucose, or with (b) nonmetabolizable L-glucose (100 mM). During systemic hypoglycemia glucagon and catecholamine concentrations promptly increased in the control animals perfused with either 100 mM L-glucose or the iso-osmotic solution lacking glucose. In contrast, glucagon, epinephrine and norepinephrine release was inhibited in the animals in which the VMH was perfused with D-glucose; hormonal secretion was partially suppressed by the VMH perfusion with 15 mM D-glucose and suppressed by approximately 85% when the VMH was perfused with 100 mM D-glucose, as compared with the control groups. We conclude that the VMH must sense hypoglycemia for full activation of catecholamine and glucagon secretion and that it is a key glucose sensor for hypoglycemic counterregulation.
腹内侧下丘脑核（VMH）对于低血糖的综合激素反应是必需的。为了确定VMH作为葡萄糖传感器的作用，我们进行了一些实验，旨在专门防止VMH中的血糖过低，同时在其他部位产生低血糖。我们使用了长期插管的清醒大鼠，其中VMH局部葡萄糖灌注（100 mM或15 mM的D-葡萄糖）与序贯正常血糖-低血糖钳夹相结合。在两个对照组中，VMH分别用（a）不含葡萄糖的等渗溶液或（b）不可代谢的L-葡萄糖（100 mM）灌注。在全身性低血糖期间，用100 mM L-葡萄糖或不含葡萄糖的等渗溶液灌注的对照动物中，胰高血糖素和儿茶酚胺浓度迅速升高。相比之下，在VMH用D-葡萄糖灌注的动物中，胰高血糖素、肾上腺素和去甲肾上腺素的释放受到抑制；与对照组相比，VMH用15 mM D-葡萄糖灌注时激素分泌受到部分抑制，而VMH用100 mM D-葡萄糖灌注时激素分泌受到约85%的抑制。我们得出结论，VMH必须感知低血糖才能充分激活儿茶酚胺和胰高血糖素的分泌，并且它是低血糖反调节的关键葡萄糖传感器。
