GLUCOSE-INTOLERANCE AND AGING - EVIDENCE FOR TISSUE INSENSITIVITY TO INSULIN
GLUCOSE-INTOLERANCE AND AGING - EVIDENCE FOR TISSUE INSENSITIVITY TO INSULIN
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DOI：
10.2337/diab.28.12.1095
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发表时间：
1979-01-01
期刊：
影响因子：
7.7
通讯作者：
DEFRONZO, RA
中科院分区：
文献类型：
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作者：
DEFRONZO, RA
在84名21-84岁的健康志愿者中，分别采用高血糖和正常血糖胰岛素钳夹技术，研究了胰岛素分泌受损和组织对胰岛素敏感性受损对衰老的葡萄糖耐受不良的相对贡献。血糖浓度急剧升高，并维持在高于基础水平的125 mg/dl 2小时。由于葡萄糖浓度保持不变，葡萄糖输注速率是葡萄糖代谢(M)的指标。在年轻受试者中，M平均为9.48 .+-。0.40 mg/kg .cntdot。与6.48相比，最小。老年受试者0.28 （P < 0.001）。当所有受试者一起考虑时，观察到M与年龄相关的进行性下降（r = -0.665, P < 0.001）。血浆胰岛素反应(I)呈双期，在前6分钟出现早期爆发，随后进入胰岛素浓度逐渐升高的阶段。在胰岛素分泌的早期和晚期，在年轻和年老的受试者之间没有观察到差异。因此，M/I（.）倍。100)，组织对内源性胰岛素的敏感性指数比值从14.90 +-下降。1.01至10.98 .+-。0.81 mg/kg .cntdot。每亩最小值。U/ml, P < 0.005。血浆胰岛素浓度急剧升高，维持在100.mu左右。U/ml高于基础水平。通过可变葡萄糖输注使血糖浓度保持在基础水平不变。M /我(同学们。100)，再次，是测量组织对胰岛素（外源性）的敏感性，并在老年人(4.95 +-。0.31毫克/公斤。每亩最小值。U/ml)比年轻(6.95 .+-。0.45)受试者（P < 0.001）。在正糖钳夹研究期间，用氚化葡萄糖测定肝葡萄糖产量；在年轻人中也有类似的下降（降至0.13 +-）。0.05 mg/kg .cntdot最小值)和最小值(到0.09。0.03 mg .cntdot。min)科目。在目前的实验条件下，通过静脉注射葡萄糖和/或胰岛素，组织对胰岛素的敏感性受损是导致糖耐量随年龄增长而下降的主要因素。由于老年受试者的肝糖生成通常被胰岛素抑制，胰岛素抵抗的部位一定位于外周组织。由高血糖钳夹技术确定的β细胞对葡萄糖的反应不能解释与年龄相关的M。
The relative contributions of impaired insulin secretion and of impaired tissue sensitivity to insulin to the glucose intolerance of aging were examined in 84 healthy volunteers, 21-84 yr of age, employing the hyperglycemic and euglycemic insulin clamp techniques, respectively. The blood glucose concentration was acutely raised and was maintained at 125 mg/dl above basal levels for 2 h. Since the glucose concentration was held constant, the glucose infusion rate was an index of glucose metabolism (M). In young subjects, M averaged 9.48 .+-. 0.40 mg/kg .cntdot. min compared with 6.48 .+-. 0.28 in old subjects (P < 0.001). When all subjects were considered together, a progressive age-related decline in M was observed (r = -0.665, P < 0.001). The plasma insulin response (I) was biphasic, with an early burst within the first 6 min, followed by a phase of gradually increasing insulin concentration. No difference in either the early or late phases of insulin secretion was observed between young and old subjects. Consequently, the M/I (.times. 100) ratio, an index of tissue sensitivity to endogenous insulin, decreased from 14.90 .+-. 1.01 to 10.98 .+-. 0.81 mg/kg .cntdot. min per .mu.U/ml (P < 0.005). The plasma insulin concentration was acutely raised and was maintained at about 100 .mu.U/ml above basal levels by a primed continuous infusion of insulin. The blood glucose concentration was held constant at the basal level by a variable glucose infusion. M/I (.times. 100), again, was a measure of tissue sensitivity to insulin (exogenous) and was decreased in old (4.95 .+-. 0.31 mg/kg .cntdot. min per .mu.U/ml) versus young (6.95 .+-. 0.45) subjects (P < 0.001). Hepatic glucose production was measured with tritiated glucose during the euglycemic clamp study; it declined similarly in young (to 0.13 .+-. 0.05 mg/kg .cntdot. min) and old (to 0.09 .+-. 0.03 mg .cntdot. min) subjects. Under the present experimental conditions, employing i.v. glucose and/or insulin, impaired tissue sensitivity to insulin is the primary factor responsible for the decrease in glucose tolerance observed with advancing age. Since hepatic glucose production is normally suppressed by insulin in old subjects, the site of insulin resitance must reside in peripheral tissues. Beta cell response to glucose, as determined by the hyperglycemic clamp technique, cannot account for the age-related decline in M.