Kahn S E, Porte D
Department of Medicine, University of Washington School of Medicine, Seattle.
Am J Med. 1988 Nov 28;85(5A):4-8. doi: 10.1016/0002-9343(88)90392-0.
Non-insulin-dependent diabetes mellitus is characterized by fasting hyperglycemia associated with defects in the pancreatic islet, the liver, and the peripheral tissues, which together comprise a feedback loop responsible for maintenance of glucose homeostasis. This review focuses on the key role of the endocrine pancreas A and B cells to coordinate glucose output from the liver with glucose utilization. The basal rate of hepatic glucose production is elevated in subjects with non-insulin-dependent diabetes mellitus and this is positively correlated with the degree of fasting hyperglycemia. This increased rate of glucose release by the liver results from impaired hepatic sensitivity to insulin and reduced insulin secretion. Though basal insulin levels in patients with non-insulin-dependent diabetes mellitus may appear normal when compared with those of healthy persons, islet function testing at matched glucose levels reveals impairments of basal and stimulated insulin secretion due to a reduction in B cell secretory capacity. The degree of impaired beta-cell responsiveness to glucose is closely related to the degree of fasting hyperglycemia but in a curvilinear fashion. The efficiency of glucose uptake by the peripheral tissues is also impaired due to a combination of decreased insulin secretion and defective cellular insulin action. This impairment becomes more important to the hyperglycemia as the islet dysfunction declines. Therapeutic interventions either improve islet dysfunction and raise plasma insulin levels, reduce hepatic glucose production, or improve the efficiency of tissue glucose uptake. All result in a decline in the fasting glucose level regardless of the cause of hyperglycemia. It is concluded that non-insulin-dependent diabetes mellitus is characterized by a steady-state re-regulation of plasma glucose concentration at an elevated level in which islet dysfunction plays a necessary role.
非胰岛素依赖型糖尿病的特征是空腹血糖升高，伴有胰岛、肝脏和外周组织的缺陷，这些共同构成了一个负责维持葡萄糖稳态的反馈回路。本综述重点关注内分泌胰腺A细胞和B细胞在协调肝脏葡萄糖输出与葡萄糖利用方面的关键作用。非胰岛素依赖型糖尿病患者的肝脏葡萄糖生成基础速率升高，且与空腹血糖升高程度呈正相关。肝脏葡萄糖释放速率增加是由于肝脏对胰岛素的敏感性受损以及胰岛素分泌减少所致。虽然与健康人相比，非胰岛素依赖型糖尿病患者的基础胰岛素水平可能看起来正常，但在匹配的血糖水平下进行胰岛功能测试时，由于B细胞分泌能力降低，显示基础和刺激胰岛素分泌均受损。β细胞对葡萄糖反应性受损的程度与空腹血糖升高程度密切相关，但呈曲线关系。由于胰岛素分泌减少和细胞胰岛素作用缺陷共同作用，外周组织对葡萄糖的摄取效率也受损。随着胰岛功能障碍的减轻，这种损害对高血糖的影响变得更加重要。治疗干预措施要么改善胰岛功能障碍并提高血浆胰岛素水平，要么减少肝脏葡萄糖生成，要么提高组织对葡萄糖的摄取效率。无论高血糖的原因如何，所有这些措施都会导致空腹血糖水平下降。结论是非胰岛素依赖型糖尿病的特征是血浆葡萄糖浓度在升高水平上的稳态重新调节，其中胰岛功能障碍起着必要作用。
