Abnormal renal, hepatic, and muscle glucose metabolism following glucose ingestion in type 2 diabetes
Abnormal renal, hepatic, and muscle glucose metabolism following glucose ingestion in type 2 diabetes
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DOI：
10.1152/ajpendo.00041.2004
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发表时间：
2004-12-01
影响因子：
5.1
通讯作者：
Gerich, JE
中科院分区：
文献类型：
--
作者：
Meyer, C;Woerle, HJ;Gerich, JE
最近的研究表明肾脏在正常人餐后葡萄糖稳态中起重要作用。为了确定其在2型糖尿病（T2 DM）餐后葡萄糖代谢异常中的作用，我们在10名T2 DM受试者和10名年龄、体重和性别匹配的非糖尿病志愿者摄入75 g葡萄糖后，联合使用双同位素技术和肾脏和骨骼肌净平衡测量。在餐后4.5小时内，糖尿病受试者的平均血糖水平升高（14.1 +/- 1.1 vs. 6.2 +/- 0.2 mM，P < 0.001），全身葡萄糖增加（100.0 ± 6.3 vs. 70.0 ± 3.3 g，P < 0.001）。后者主要是由于内源性葡萄糖释放量增加了23 g（39.8 ± 5.9 vs. 17.0 ± 1.8 g，P < 0.002），因为摄入葡萄糖的全身表现仅增加了0.77 g（60.2 ± 1.4 vs. 53.0 ± 2.2 g，P < 0.02）。大约40%的糖尿病受试者的内源性葡萄糖释放增加是由于肾脏葡萄糖释放增加（19.6 +/- 3.1对10.6 +/- 2.4 g，P < 0.05）。糖尿病患者餐后全身组织葡萄糖摄取也增加（82.3 ± 4.7比69.8 ± 3.5 g，P < 0.05），分布改变;肾脏葡萄糖摄取增加（21.0 ± 3.5 vs. 9.8 ± 2.3 g，P < 0.03），而肌肉葡萄糖摄取正常（18.5 ± 1.8 vs. 25.9 ± 3.3 g，P = 0.16）。我们的结论是，在T2 DM中，1）肝脏和肾脏都有助于餐后葡萄糖的过度产生，2）餐后肾脏葡萄糖摄取增加，导致肌肉和肾脏对葡萄糖处置的相对重要性发生变化。后者可能为糖尿病的肾脏糖原积聚特征以及高血糖导致糖尿病肾病的机制提供了解释。
Recent studies indicate an important role of the kidney in postprandial glucose homeostasis in normal humans. To determine its role in the abnormal postprandial glucose metabolism in type 2 diabetes mellitus (T2DM), we used a combination of the dual-isotope technique and net balance measurements across kidney and skeletal muscle in 10 subjects with T2DM and 10 age-, weight-, and sex-matched nondiabetic volunteers after ingestion of 75 g of glucose. Over the 4.5-h postprandial period, diabetic subjects had increased mean blood glucose levels (14.1 +/- 1.1 vs. 6.2 +/- 0.2 mM, P < 0.001) and increased systemic glucose appearance (100.0 ± 6.3 vs. 70.0 ± 3.3 g, P < 0.001). The latter was mainly due to similar to23 g greater endogenous glucose release (39.8 +/- 5.9 vs. 17.0 +/- 1.8 g, P < 0.002), since systemic appearance of the ingested glucose was increased by only ∼7 g (60.2 ± 1.4 vs. 53.0 ± 2.2 g, P < 0.02). Approximately 40% of the diabetic subjects' increased endogenous glucose release was due to increased renal glucose release (19.6 +/- 3.1 vs. 10.6 +/- 2.4 g, P < 0.05). Postprandial systemic tissue glucose uptake was also increased in the diabetic subjects (82.3 ± 4.7 vs. 69.8 ± 3.5 g, P < 0.05), and its distribution was altered; renal glucose uptake was increased (21.0 +/- 3.5 vs. 9.8 +/- 2.3 g, P < 0.03), whereas muscle glucose uptake was normal (18.5 ± 1.8 vs. 25.9 ± 3.3 g, P = 0.16). We conclude that, in T2DM, 1) both liver and kidney contribute to postprandial overproduction of glucose, and 2) postprandial renal glucose uptake is increased, resulting in a shift in the relative importance of muscle and kidney for glucose disposal. The latter may provide an explanation for the renal glycogen accumulation characteristic of diabetes mellitus as well as a mechanism by which hyperglycemia may lead to diabetic nephropathy.