Pagano G, Cassader M, Cavallo-Perin P, Bruno A, Masciola P, Ozzello A, Dall'Omo A M, Foco A
Metabolism. 1984 Nov;33(11):976-81. doi: 10.1016/0026-0495(84)90223-3.
It has recently been made clear that reduced sensitivity to exogenous insulin can be demonstrated in the course of aging. This phenomenon has been further investigated with the aid of sophisticated techniques, such as the euglycemic clamp, which, when coupled with the measurement of hepatic glucose production, showed that "impaired tissue sensitivity to insulin is the primary factor responsible for the decrease of glucose tolerance in advancing age." Nevertheless, this study did not establish whether such impairment reflects reduced sensitivity (receptor deficiency) or reduced response (postreceptor or receptor plus postreceptor defect), as shown in other diseases. Evidence in favor of the view that receptor deficiency is responsible can be seen in our observation of an approximately 50% reduction in receptors in a study of insulin binding on isolated human fat cells. Two aspects of this question appeared to require further investigation: tissue sensitivity to receptor-saturating insulin concentration (euglycemic clamp at about 1000 microU/mL plasma insulin), and the glucose transport system coupled to the receptor. A decrease in receptors alone should shift the insulin sensitivity curve to the right, both in vivo (euglycemic clamp) and in vitro (glucose transport), with no reduction of the maximum effect. A solution to this question is proposed in the light of a study conducted on young volunteers and subjects over 65 years old.
最近已经明确，在衰老过程中可表现出对外源性胰岛素的敏感性降低。借助复杂技术，如正常血糖钳夹技术，对这一现象进行了进一步研究。当与肝葡萄糖生成的测量相结合时，该技术表明“组织对胰岛素敏感性受损是导致老年时糖耐量降低的主要因素”。然而，这项研究并未确定这种损害是否反映了敏感性降低（受体缺陷）或反应降低（受体后或受体加受体后缺陷），正如在其他疾病中所显示的那样。在一项对分离的人体脂肪细胞上胰岛素结合的研究中，我们观察到受体减少了约50%，这一观察结果支持受体缺陷起作用的观点。这个问题的两个方面似乎需要进一步研究：组织对受体饱和胰岛素浓度的敏感性（血浆胰岛素约1000微单位/毫升时的正常血糖钳夹），以及与受体偶联的葡萄糖转运系统。仅受体减少应会使胰岛素敏感性曲线在体内（正常血糖钳夹）和体外（葡萄糖转运）均向右移动，而最大效应不降低。根据一项针对年轻志愿者和65岁以上受试者的研究，提出了这个问题的解决方案。
