MECHANISMS OF INSULIN RESISTANCE IN AGING
MECHANISMS OF INSULIN RESISTANCE IN AGING
复制标题
DOI：
10.1172/jci110908
复制
发表时间：
1983-01-01
影响因子：
15.9
通讯作者：
OLEFSKY, JM
中科院分区：
文献类型：
--
作者：
FINK, RI;KOLTERMAN, OG;OLEFSKY, JM
17名老年人和27名非老年人，非肥胖受试者(平均年龄69。+-。1和37。+-。分别为2年)，以评估与衰老相关的碳水化合物耐量异常的机制。在75g口服葡萄糖耐量试验中，与非老年受试者相比，老年受试者的血糖和胰岛素水平显著升高，这表明他们处于胰岛素抵抗状态。在胰岛素输注速率为40mU/m2/min的条件下，两组患者均采用正常血糖葡萄糖钳夹技术检测外周胰岛素敏感性。相似的稳态血清胰岛素水平导致外周血糖处理率为151.+-。老年人为每分钟17 mg/m~2，为247.+-。非老年组为12 mg/m~2/min，说明老年人群存在胰岛素抵抗。在老年组和非老年组中，胰岛素与分离的脂肪细胞和单核细胞的结合相似(2.34。+-)。0.33比2.62+-0.24%和5.04。+-。1.10比5.12+-1.07%)。因此，胰岛素结合正常的胰岛素抵抗提示胰岛素作用存在受体后缺陷。通过使用每分钟15和1200 mU/m2的输液速率进行额外的正常血糖钳夹研究来评估剂量-反应关系的等高线，证实了这一点。这些研究表明，老年受试者的葡萄糖处理率分别下降了39%和25%。结果证实了受体后缺陷的存在和剂量-反应曲线的右移。在以每分钟15mU/m~2的速度输注胰岛素时，老年受试者S抑制肝脏葡萄糖输出的能力较弱(77。5比89。+-。4%抑制)，但在40和1200 mU/m~2/min输注时，两组的肝脏葡萄糖输出均受到完全和同等的抑制。老年受试者个体的糖耐量与外周胰岛素抵抗程度呈显著负相关(r=0.59，P<；0.01)，糖耐量试验中的2 h血糖水平反映的是糖耐量，而外周胰岛素抵抗的程度则是通过40 mU/m2/min的胰岛素输注中的葡萄糖处理率来评估。碳水化合物不耐受显然是衰老过程的一部分。这种碳水化合物不耐受似乎是外周胰岛素抵抗的结果，这种外周胰岛素抵抗是由于靶组织胰岛素作用的受体后缺陷，导致外周葡萄糖处置的最大速率降低和胰岛素作用剂量-反应曲线右移。在老年人中，糖耐量异常的严重程度与外周胰岛素抵抗的程度直接相关。
Seventeen elderly and 27 non-elderly, nonobese subjects (mean age 69 .+-. 1 and 37 .+-. 2 yr, respectively) were studied to assess the mechanisms responsible for the abnormal carbohydrate tolerance associated with aging. Serum glucose and insulin levels were significantly elevated in the elderly subjects compared with the nonelderly subjects during a 75 g oral glucose tolerance test, suggesting an insulin resistant state. Peripheral insulin sensitivity was assessed in both groups using the euglycemic glucose clamp technique during an insulin infusion rate of 40 mU/m2 per min. Similar steady-state serum insulin levels led to a peripheral glucose disposal rate of 151 .+-. 17 mg/m2 per min in the elderly compared with a value of 247 .+-. 12 mg/m2 per min in the nonelderly, thus documenting the presence of insulin resistance in the elderly subjects. Insulin binding to isolated adipocytes and monocytes was similar in the elderly and nonelderly groups (2.34 .+-. 0.33 vs. 2.62 .+-. 0.24% and 5.04 .+-. 1.10 vs. 5.12 .+-. 1.07%), respectively. Thus, insulin resistance in the presence of normal insulin binding suggests the presence of a postreceptor defect in insulin action. This was confirmed by performing additional euglycemic clamp studies using infusion rates of 15 and 1200 mU/m2 per min to assess the contours of the dose-response relationships. These studies revealed a 39 and 25% decrease in the glucose disposal rate in the elderly subjects, respectively. The results confirm the presence of a postreceptor defect and a rightward shift in the dose-response curve. Insulin''s ability to suppress hepatic glucose output was less in the elderly subjects during the 15 mU/m2 per min insulin infusion (77 .+-. 5 vs. 89 .+-. 4% suppression), but hepatic glucose output was fully and equally suppressed in both groups during the 40 and 1200 mU/m2 per min infusion. A significant inverse relationship was observed between the degree of glucose intolerance in the individual elderly subjects, as reflected by the 2 h serum glucose level during the oral glucose tolerance test, and the degree of peripheral insulin resistance as assessed by the glucose disposal rate during the 40 mU/m2 per min insulin infusion (r =0.59, P < 0.01). Carbohydrate intolerance evidently develops as part of the aging process. This carbohydrate intolerance appears to be the consequence of peripheral insulin resistance caused by a postreceptor defect in target tissue insulin action, which causes both a decrease in the maximal rate of peripheral glucose disposal and a rightward shift in the insulin action dose-response curve. In elderly subjects, the severity of the abnormality in carbohydrate tolerance is directly correlated to the degree of peripheral insulin resistance.