Thorburn A W, Gumbiner B, Bulacan F, Wallace P, Henry R R
Department of Medicine, University of California, San Diego.
J Clin Invest. 1990 Feb;85(2):522-9. doi: 10.1172/JCI114468.
To examine whether reduced rates of oxidative (Gox) and non-oxidative (Nox) glucose metabolism in non-insulin-dependent diabetes mellitus (NIDDM) are due to reduced glucose uptake, intrinsic defects in intracellular glucose metabolism or increased fat oxidation (Fox), indirect calorimetry was performed at similar glucose uptake rates in eight nonobese NIDDM and eight comparable nondiabetic subjects. Three glucose clamp studies were performed: one in the nondiabetic and two in the NIDDM subjects. In the nondiabetic subjects, glucose uptake was increased to 7.62 +/- 0.62 mg/kg of fat-free mass (FFM) per min by increasing serum insulin to 309 pmol/liter at a glucose concentration of 5.1 mmol/liter. By raising the concentration of either serum glucose or insulin fourfold in the NIDDM subjects, glucose uptake was matched to nondiabetic subjects (8.62 +/- 0.49 and 8.59 +/- 0.51 mg/kg FFM per min, respectively, P = NS). Skeletal muscle glycogen synthase activity and plasma lactate levels were measured to characterize Nox. When glucose uptake was matched to nondiabetics by hyperglycemia or hyperinsulinemia, Gox was reduced by 26-28% in NIDDM (P less than 0.025) whereas Fox was similar. Nox was greater in NIDDM (P less than 0.01) and was accompanied by increases in circulating lactate levels. Glycogen synthase activity was reduced by 41% (P less than 0.025) when glucose uptake was matched by hyperglycemia. Glycogen synthase activity was normalized in NIDDM, however, when glucose uptake was matched by hyperinsulinemia. Therefore, a defect in Gox exists in nonobese NIDDM subjects which cannot be overcome by increasing glucose uptake or insulin. Since both glucose uptake and Fox were similar in the two subject groups these factors were not responsible for reduced Gox. Increased Nox in NIDDM is primarily into lactate. Reduced glycogen synthase activity in NIDDM is independent of glucose uptake but can be overcome by increasing the insulin concentration.
为了研究非胰岛素依赖型糖尿病（NIDDM）患者氧化（Gox）和非氧化（Nox）葡萄糖代谢率降低是由于葡萄糖摄取减少、细胞内葡萄糖代谢的内在缺陷还是脂肪氧化增加（Fox），我们对8名非肥胖NIDDM患者和8名可比的非糖尿病受试者在相似的葡萄糖摄取率下进行了间接测热法。进行了三项葡萄糖钳夹研究：一项在非糖尿病受试者中，两项在NIDDM受试者中。在非糖尿病受试者中，在葡萄糖浓度为5.1 mmol/升时，通过将血清胰岛素增加到309 pmol/升，葡萄糖摄取增加到7.62±0.62 mg/kg无脂肪体重（FFM）每分钟。通过将NIDDM受试者的血清葡萄糖或胰岛素浓度提高四倍，使葡萄糖摄取与非糖尿病受试者相匹配（分别为8.62±0.49和8.59±0.51 mg/kg FFM每分钟，P = NS）。测量骨骼肌糖原合酶活性和血浆乳酸水平以表征Nox。当通过高血糖或高胰岛素血症使葡萄糖摄取与非糖尿病患者相匹配时，NIDDM患者的Gox降低了26 - 28%（P < 0.025），而Fox相似。NIDDM患者的Nox更高（P < 0.01），并伴有循环乳酸水平升高。当通过高血糖使葡萄糖摄取相匹配时，糖原合酶活性降低了41%（P < 0.025）。然而，当通过高胰岛素血症使葡萄糖摄取相匹配时，NIDDM患者的糖原合酶活性恢复正常。因此，非肥胖NIDDM患者存在Gox缺陷，这不能通过增加葡萄糖摄取或胰岛素来克服。由于两个受试者组的葡萄糖摄取和Fox都相似，这些因素不是Gox降低的原因。NIDDM患者中Nox增加主要转化为乳酸。NIDDM患者中糖原合酶活性降低与葡萄糖摄取无关，但可以通过增加胰岛素浓度来克服。
Zotero 插件
