Nankervis A, Proietto J, Aitken P, Harewood M, Alford F
Diabetologia. 1982 Oct;23(4):320-5. doi: 10.1007/BF00253737.
Hepatic glucose production and metabolic clearance rate of glucose were measured using (3-3H) glucose at steady state, basally and during two sequential 2 h insulin (25 and 40 mU . kg -1 . h -1)/glucose (2 and 3 mg. kg -1 . min -1) infusion periods. Eight diabetic subjects were studied before and after 1 week of twice daily insulin therapy; six control subjects matched for age, weight and degree of obesity were also studied. In the diabetic patients, pre-treatment hepatic glucose production was 20.0 +/- 2.2, 9.9 +/- 2.9, and 1.4 +/- 0.8 mu mol . kg -1 . min -1 respectively (+/- SEM) for each of the three periods, and fell significantly with treatment to 12.8 +/- 1.7, 4.0 +/- 1.5 and 1.9 +/- 1.0 mu mol . kg -1 . min -1. Hepatic glucose production in normal subjects was 13.2 +/- 0.6, 2.2 +/- 0.8 and less than 1 mu mol . kg -1 . min -1. The pre-treatment metabolic clearance rate in all diabetic studies with insulin levels greater than or equal to 30 mU/l was 1.10 +/- 0.14 ml . kg -1 . min -1 and remained virtually unchanged following insulin therapy; this was significantly lower than in the control subjects (6.83 +/- 1.02, p less than 0.001). Basal non-esterified fatty acid levels were higher (p less than 0.02) in the pre-treated diabetic patients compared to post-treated diabetic patients and control subjects. Non-esterified fatty acids in each group fell to similar levels during the insulin infusions, but the rate of fall was slower in the pre-treated diabetic patients. Insulin receptor binding to erythrocytes was normal in the diabetic subjects and unchanged by treatment. Therefore, following insulin treatment of uncontrolled Type 2 (non-insulin-dependent) diabetes, the initially increased basal hepatic glucose production, and decreased hepatic sensitivity, return towards normal. However, the glucose clearance remains low, despite good diabetic control, and appears to be a major factor in the continuing glucose intolerance. As insulin receptor binding is normal, the defect of glucose clearance in Type 2 diabetes appears compatible with a post-receptor defect of glucose metabolism.
在稳定状态下，基础状态以及在两个连续的2小时胰岛素（25和40 mU·kg⁻¹·h⁻¹）/葡萄糖（2和3 mg·kg⁻¹·min⁻¹）输注期间，使用（3-³H）葡萄糖测量肝脏葡萄糖生成和葡萄糖代谢清除率。对8名糖尿病患者在每日两次胰岛素治疗1周前后进行了研究；还研究了6名年龄、体重和肥胖程度相匹配的对照受试者。在糖尿病患者中，三个时期的治疗前肝脏葡萄糖生成分别为20.0±2.2、9.9±2.9和1.4±0.8 μmol·kg⁻¹·min⁻¹（±SEM），治疗后显著下降至12.8±1.7、4.0±1.5和1.9±1.0 μmol·kg⁻¹·min⁻¹。正常受试者的肝脏葡萄糖生成分别为13.2±0.6、2.2±0.8和小于1 μmol·kg⁻¹·min⁻¹。在所有胰岛素水平大于或等于30 mU/l的糖尿病研究中，治疗前的代谢清除率为1.10±0.14 ml·kg⁻¹·min⁻¹，胰岛素治疗后基本保持不变；这显著低于对照受试者（6.83±1.02，p＜0.001）。治疗前糖尿病患者的基础非酯化脂肪酸水平高于治疗后糖尿病患者和对照受试者（p＜0.02）。在胰岛素输注期间，每组的非酯化脂肪酸水平均降至相似水平，但治疗前糖尿病患者的下降速度较慢。糖尿病患者红细胞上的胰岛素受体结合正常，且治疗后无变化。因此，在对未控制的2型（非胰岛素依赖型）糖尿病进行胰岛素治疗后，最初升高的基础肝脏葡萄糖生成和降低的肝脏敏感性恢复正常。然而，尽管糖尿病得到了良好控制，但葡萄糖清除率仍然较低，这似乎是持续葡萄糖不耐受的一个主要因素。由于胰岛素受体结合正常，2型糖尿病中葡萄糖清除缺陷似乎与葡萄糖代谢的受体后缺陷相符。
