Consoli A, Nurjhan N, Reilly J J, Bier D M, Gerich J E
Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15261.
J Clin Invest. 1990 Dec;86(6):2038-45. doi: 10.1172/JCI114940.
To assess the mechanisms responsible for increased gluconeogenesis in noninsulin-dependent diabetes mellitus (NIDDM), we infused [3-14C]lactate, [3-13C]alanine, and [6-3H]glucose in 10 postabsorptive NIDDM subjects and in 9 age- and weight-matched nondiabetic volunteers and measured systemic appearance of alanine and lactate, their release from forearm tissues, and their conversion into plasma glucose (corrected for Krebs cycle carbon exchange). Systemic appearance of lactate and alanine were both significantly greater in diabetic subjects (18.2 +/- 0.9 and 5.8 +/- 0.4 mumol/kg/min, respectively) than in the nondiabetic volunteers (12.6 +/- 0.7 and 4.2 +/- 0.3 mumol/kg/min, respectively, P less than 0.001 and P less than 0.01). Conversions of lactate and alanine to glucose were also both significantly greater in NIDDM subjects (8.6 +/- 0.5 and 2.4 +/- 0.1 mumole/kg/min, respectively) than in nondiabetic volunteers (4.2 +/- 0.4 and 1.8 +/- 0.1 mumol/kg/min, respectively, P less than 0.001 and P less than 0.025). The proportion of systemic alanine appearance converted to glucose was not increased in NIDDM subjects (42.7 +/- 1.9 vs. 44.2 +/- 2.9% in nondiabetic volunteers), whereas the proportion of systemic lactate appearance converted to glucose was increased in NIDDM subjects (48.3 +/- 3.8 vs. 34.2 +/- 3.8% in nondiabetic volunteers, P less than 0.025); the latter increased hepatic efficiency accounted for approximately 40% of the increased lactate conversion to glucose. Neither forearm nor total body muscle lactate and alanine release was significantly different in NIDDM and nondiabetic volunteers. Therefore, we conclude that increased substrate delivery to the liver and increased efficiency of intrahepatic substrate conversion to glucose are both important factors for the increased gluconeogenesis of NIDDM and that tissues other than muscle are responsible for the increased delivery of gluconeogenic precursors to the liver.
为评估非胰岛素依赖型糖尿病（NIDDM）中糖异生增加的机制，我们对10名空腹的NIDDM受试者以及9名年龄和体重匹配的非糖尿病志愿者输注了[3-14C]乳酸、[3-13C]丙氨酸和[6-3H]葡萄糖，并测量了丙氨酸和乳酸的全身出现率、它们从前臂组织的释放以及它们转化为血浆葡萄糖的情况（校正了三羧酸循环碳交换）。糖尿病受试者中乳酸和丙氨酸的全身出现率均显著高于非糖尿病志愿者（分别为18.2±0.9和5.8±0.4μmol/kg/min）（分别为12.6±0.7和4.2±0.3μmol/kg/min，P<0.001和P<0.01）。NIDDM受试者中乳酸和丙氨酸转化为葡萄糖的比例也均显著高于非糖尿病志愿者（分别为8.6±0.5和2.4±0.1μmol/kg/min）（分别为4.2±0.4和1.8±0.1μmol/kg/min，P<0.001和P<0.025）。NIDDM受试者中全身丙氨酸出现后转化为葡萄糖的比例没有增加（非糖尿病志愿者为42.7±1.9%对44.2±2.9%），而NIDDM受试者中全身乳酸出现后转化为葡萄糖的比例增加了（非糖尿病志愿者为48.3±3.8%对34.2±3.8%，P<0.025）；后者肝脏效率的提高约占乳酸转化为葡萄糖增加量的40%。NIDDM受试者与非糖尿病志愿者在前臂或全身肌肉中乳酸和丙氨酸的释放均无显著差异。因此，我们得出结论，底物向肝脏输送的增加以及肝内底物转化为葡萄糖效率的提高都是NIDDM中糖异生增加的重要因素，并且肌肉以外的组织负责向肝脏输送更多的糖异生前体。
