Hetenyi G, Gauthier C, Byers M, Vranic M
Department of Physiology, School of Medicine, University of Ottawa, Toronto, Canada.
Am J Physiol. 1989 Feb;256(2 Pt 1):E277-83. doi: 10.1152/ajpendo.1989.256.2.E277.
The plasma concentration of glucagon (IRG), catecholamines, and hepatic glucose production (Ra) were followed in insulin-induced hypoglycemia in dogs before (normal) and at 14-21 and again at 89-119 days after the injection of alloxan (diabetic). Some diabetic dogs were also tested when euglycemia was restored by phlorizin. In the normal state plasma IRG and epinephrine were raised by a factor of 3 and 15, respectively. Ra increased in two phases, an early peak (350% basal) was followed by a plataeu at about twice basal. In diabetes, irrespective of its duration, plasma IRG was decreased in hypoglycemia, and the rise in plasma epinephrine was significantly reduced. Ra remained unchanged. In phlorizin-treated euglycemic diabetic dogs plasma IRG fell, and the response in plasma epinephrine remained blunted. There was no early rise in Ra, but the same elevated plateau was reached at the same time as in normal animals. In conclusion, the following is observed in diabetic dogs. 1) The sensitivity of alpha-cells to insulin is maintained, but that to hypoglycemia is lost. The concentration of plasma catecholamines is raised less than in normals. With no increase in plasma glucagon this rise is not sufficient to increase Ra. 2) Restoration of euglycemia with phlorizin does not restore normal IRG and epinephrine responses to hypoglycemia but restores the delayed increase of Ra. Thus the restoration of euglycemia in severely diabetic dogs partially restores the responses of the liver, but not of the alpha-cell or sympathetic discharge, to hypoglycemia.
在犬胰岛素诱导的低血糖症中，分别于注射四氧嘧啶前（正常状态）、注射后14 - 21天以及89 - 119天（糖尿病状态），对胰高血糖素（免疫反应性胰高血糖素，IRG）、儿茶酚胺的血浆浓度以及肝葡萄糖生成率（Ra）进行了跟踪监测。部分糖尿病犬在通过根皮苷恢复血糖正常时也进行了检测。在正常状态下，血浆IRG和肾上腺素分别升高至原来的3倍和15倍。Ra分两个阶段升高，早期出现一个峰值（为基础值的350%），随后维持在约基础值两倍的平台期。在糖尿病状态下，无论病程长短，低血糖时血浆IRG均降低，血浆肾上腺素的升高也显著减少。Ra保持不变。在根皮苷治疗的血糖正常的糖尿病犬中，血浆IRG下降，血浆肾上腺素的反应仍受到抑制。Ra没有早期升高，但与正常动物同时达到相同的升高平台期。总之，在糖尿病犬中观察到以下情况。1）α细胞对胰岛素的敏感性得以维持，但对低血糖的敏感性丧失。血浆儿茶酚胺浓度的升高低于正常动物。由于血浆胰高血糖素没有增加，这种升高不足以使Ra升高。2）用根皮苷恢复血糖正常并不能恢复IRG和肾上腺素对低血糖的正常反应，但能恢复Ra的延迟升高。因此，在严重糖尿病犬中恢复血糖正常可部分恢复肝脏对低血糖的反应，但不能恢复α细胞或交感神经放电对低血糖的反应。
