Vranic M, Wajngot A, Efendic S
Adv Exp Med Biol. 1985;189:227-45. doi: 10.1007/978-1-4757-1850-8_13.
Insulin resistance has been measured in man by nonsteady state tracer methodology. Increase in overall glucose utilization and suppression of glucose production was measured when hyperglycemia was achieved either by infusing glucagon or glucose. With the first method, insulin resistance was assessed in obese man and in lean hypertriglyceridemic patients. With the second method, insulin resistance was assessed in lean mild type II diabetics. These methodologies can only assess deficiences in overall glucose utilization and glucose production, but cannot delineate the defect in glucose uptake by the liver. However, if a given metabolic event is essentially characteristic of only one organ, metabolic abnormalities specific to that organ can be detected in vivo provided there is a probe specific to that metabolic pathway. Therefore, in lean mild type II diabetics the liver glucose futile cycle was assessed by a double tracer method. Previously it was shown that liver glucose futile cycling is increased in diabetic dogs. In healthy control subjects in basal state and during glucose infusion, the futile cycle could not be detected, but it represented a major part of glucose metabolism in liver of type II diabetics. It appears, therefore, that most of the glucose taken up by the liver during the glucose challenge in diabetics reenters the blood stream without being oxidized or polymerized. On the basis of these studies, it was concluded that excessive hyperglycemia in the diabetics during glucose infusion is due to a decrease in irreversible glucose uptake (impaired phosphorylation and futile cycling) and to a decrease in suppression of glucose production. The relative contribution of the liver and periphery to hyperglycemia seems to be almost equivalent. The mechanism behind the increased glucose cycle activity is not clear. It may be due to a relative decrease of glycogen synthase or increase in glucose-6-phosphatase or both. These observations in mild lean type II diabetics may have implications also in some other types of diabetes, since we have observed that futile cycling is even more marked in obese type II diabetics and that it could account in part for the diabetogenic effect of growth hormone in acromegalics.
胰岛素抵抗已通过非稳态示踪方法在人体中进行测量。当通过输注胰高血糖素或葡萄糖实现高血糖时，测量总体葡萄糖利用率的增加和葡萄糖生成的抑制情况。使用第一种方法，在肥胖男性和瘦型高甘油三酯血症患者中评估胰岛素抵抗。使用第二种方法，在轻度II型糖尿病瘦患者中评估胰岛素抵抗。这些方法只能评估总体葡萄糖利用和葡萄糖生成方面的缺陷，但无法描绘肝脏葡萄糖摄取的缺陷。然而，如果给定的代谢事件本质上仅为一个器官所特有，那么只要有针对该代谢途径的探针，就可以在体内检测到该器官特有的代谢异常。因此，在轻度II型糖尿病瘦患者中，通过双示踪法评估肝脏葡萄糖无效循环。此前已表明糖尿病犬的肝脏葡萄糖无效循环增加。在基础状态和葡萄糖输注期间的健康对照受试者中，无法检测到无效循环，但它在II型糖尿病患者肝脏的葡萄糖代谢中占主要部分。因此，似乎在糖尿病患者葡萄糖激发试验期间肝脏摄取的大部分葡萄糖在未被氧化或聚合的情况下重新进入血流。基于这些研究，得出结论，糖尿病患者在葡萄糖输注期间的过度高血糖是由于不可逆葡萄糖摄取减少（磷酸化受损和无效循环）以及葡萄糖生成抑制减少所致。肝脏和外周对高血糖的相对贡献似乎几乎相等。葡萄糖循环活性增加背后的机制尚不清楚。这可能是由于糖原合酶相对减少或葡萄糖-6-磷酸酶增加或两者兼而有之。在轻度II型糖尿病瘦患者中的这些观察结果可能对其他一些类型的糖尿病也有影响，因为我们观察到无效循环在肥胖II型糖尿病患者中更为明显，并且它可能部分解释肢端肥大症患者中生长激素的致糖尿病作用。
