QUANTIFICATION OF THE RELATIVE IMPAIRMENT IN ACTIONS OF INSULIN ON HEPATIC GLUCOSE-PRODUCTION AND PERIPHERAL GLUCOSE-UPTAKE IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS
QUANTIFICATION OF THE RELATIVE IMPAIRMENT IN ACTIONS OF INSULIN ON HEPATIC GLUCOSE-PRODUCTION AND PERIPHERAL GLUCOSE-UPTAKE IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS
复制标题
DOI：
10.1016/0026-0495(88)90023-6
复制
发表时间：
1988-01-01
影响因子：
9.8
通讯作者：
GERICH, JE
中科院分区：
文献类型：
--
作者：
CAMPBELL, PJ;MANDARINO, LJ;GERICH, JE
在非胰岛素依赖型糖尿病（NIDDM）中，肝脏和外周组织都对胰岛素有抵抗，但这些异常对空腹高血糖的相对严重程度和贡献尚不清楚。因此，我们在14名NIDDM受试者和14名年龄和体重匹配的非糖尿病志愿者（NV）中，使用葡萄糖钳序次胰岛素输注技术以及葡萄糖通量的同位素估计，确定了胰岛素介导的肝糖生成（GP）抑制和外周糖摄取（GU）刺激的剂量反应特征。两种GP的吸收后率均为94 .+-。7 v 72 +-。NV为2 mg/M2/min， P < 0.01)， GU为88。5 v 72 +-。在NIDDM组中，2 （P < 0.01）显著升高。NIDDM患者血浆胰岛素半有效浓度（ED50）对GP的抑制作用（64 +-）。14 .mu。U/mL)和对GU的刺激(118 .+-。20 .mu。U/mL)均比正常水平（26 .+-）增加2倍以上。2和58，+-。5 .mu。U/mL，两者均P < 0.01)，且呈极显著相关（r = 0.68, P < 0.01）。虽然在NIDDM受试者中GP可以被完全抑制，但他们的最大GU降低了30%（287 +-）。20 v 372。NV为15 mg/m2/min， P < 0.01)。然而，在所有与生理相关的血浆胰岛素浓度研究中，GP和GU反应都有相当的损害。此外，NIDDM患者的空腹血糖浓度与GP基础率升高高度相关（r = 0.81, P < 0.005），但与GU降低无关。我们得出结论，NIDDM患者的肝脏和外周组织对胰岛素具有相同的抗性。由于胰岛素对吸收后状态下的肝脏GP有明显的抑制作用，只有20%至30%的GU是胰岛素介导的，我们的研究结果表明，肝脏而非外周胰岛素抵抗是导致这种疾病中空腹高血糖的主要因素。
In non-insulin-dependent diabetes mellitus (NIDDM), both liver and peripheral tissues are resistant to insulin, but the relative severity and contribution of these abnormalities to fasting hyperglycemia are poorly understood. We, therefore, determined the dose-response characteristics for insulin-mediated suppression of hepatic glucose production (GP) and stimulation of peripheral glucose uptake (GU) in 14 NIDDM subjects and 14 age- and weight-matched nondiabetic volunteers (NV) using the glucose clamp sequential insulin infusion technique along with isotopic estimation of glucose flux. Postabsorptive rates of both GP (94 .+-. 7 v 72 .+-. 2 mg/M2/min in NV, P < .01) and GU (88 .+-. 5 v 72 .+-. 2 in NV, P < .01) were significantly increased in NIDDM subjects. The ED50 (half-maximally effective plasma insulin concentration) in NIDDM subjects for suppression of GP (64 .+-. 14 .mu.U/mL) and stimulation of GU (118 .+-. 20 .mu.U/mL) were both increased more than twofold above normal (26 .+-. 2 and 58 .+-. 5 .mu.U/mL, respectively, both P < .01) and were significantly correlated with one another (r = .68, P < .01). Although GP could be totally suppressed in the NIDDM subjects, their maximal GU was reduced 30% (287 .+-. 20 v 372 .+-. 15 mg/m2/min in NV, P < .01). Nevertheless, at all physiologically relevant plasma insulin concentrations studied, there was comparable impairment in GP and GU responses. Moreover, fasting plasma glucose concentrations in NIDDM subjects were highly correlated with their increased basal rates of GP (r = .81, P < .005) but not with their reduced GU. We conclude that hepatic and peripheral tissues are equally resistant to insulin in NIDDM. Because insulin exerts an appreciable suppressive effect on hepatic GP in the postabsorptive state when only 20% to 30% of GU is insulin-mediated, our findings suggest that hepatic, rather than peripheral, insulin resistance is the major factor responsible for fasting hyperglycemia in this disorder.