Unger R H, Orci L
Arch Intern Med. 1977 Apr;137(4):482-91.
The glucagon-secreting A cell is a vital component of the organ system which regulates the distribution of fuel--the islets of Langerhans. Bihormonal control of glucoregulation through a push-pull system maintains the glucose concentration of extracellular fluid within narrow limits irrespective of glucose flux rates through relative equality of glucose influx and efflux. This equality requires appropriate secretion mixtures of the biologic antagonists, insulin and glucagon, directed by a glucose sensor. In severe diabetes, there are virtually no B cells and A cells are in contact largely with other A cells and their glucose-sensing capacity is lost. The A cell hypersecretes and in most juvenile type diabetics aggressive therapy with insulin fails to restore it to normal. Glucagon is a factor in the development of endogenous hyperglycemia, and ketoacidosis. Its suppression may provide a possible approach in the future pharmacologic management of diabetic hyperglycemia.
分泌胰高血糖素的A细胞是调节燃料分配的器官系统——胰岛的重要组成部分。通过推挽系统对葡萄糖调节进行双激素控制,可将细胞外液的葡萄糖浓度维持在狭窄范围内,而不论葡萄糖通量率如何,这是通过葡萄糖流入和流出的相对平衡实现的。这种平衡需要由葡萄糖传感器指导的生物拮抗剂胰岛素和胰高血糖素的适当分泌混合物。在严重糖尿病中,实际上没有B细胞,A细胞主要与其他A细胞接触,并且它们的葡萄糖传感能力丧失。A细胞分泌过多,在大多数青少年型糖尿病患者中,积极的胰岛素治疗未能使其恢复正常。胰高血糖素是内源性高血糖和酮症酸中毒发展的一个因素。抑制胰高血糖素可能为未来糖尿病高血糖的药物治疗提供一种可能的方法。