MECHANISM OF INCREASED GLUCONEOGENESIS IN NONINSULIN-DEPENDENT DIABETES-MELLITUS - ROLE OF ALTERATIONS IN SYSTEMIC, HEPATIC, AND MUSCLE LACTATE AND ALANINE METABOLISM
MECHANISM OF INCREASED GLUCONEOGENESIS IN NONINSULIN-DEPENDENT DIABETES-MELLITUS - ROLE OF ALTERATIONS IN SYSTEMIC, HEPATIC, AND MUSCLE LACTATE AND ALANINE METABOLISM
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DOI：
10.1172/jci114940
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发表时间：
1990-12-01
影响因子：
15.9
通讯作者：
GERICH, JE
中科院分区：
文献类型：
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作者：
CONSOLI, A;NURJHAN, N;GERICH, JE
为了评估非胰岛素依赖型糖尿病（NIDDM）中糖异生增加的机制，我们在10名吸收后的NIDDM受试者和9名年龄和体重匹配的非糖尿病志愿者中注入了[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表现、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（根据Krebs循环碳交换进行了校正）。在糖尿病患者中，乳酸和丙氨酸对葡萄糖的全身性表现也显著增加（18.2 .+-）。0.9和5.8 .+。0.4 .mu。Mol /kg/min)比非糖尿病志愿者(12.6。0.7和4.2 .+-。0.3 .mu。mol/kg/min, P < 0.001和P < 0.01)。NIDDM患者乳酸和丙氨酸向葡萄糖的转化也显著增加（8.6 .+-）。0.5和2.4 .+-。0.1 .mu。mol /kg/min)比非糖尿病志愿者(4.2。0.4和1.8 .+-。0.1 .mu。mol/kg/min, P < 0.001和P < 0.025)。在NIDDM受试者中，系统丙氨酸外观转化为葡萄糖的比例增加（42.7 +-）。1.9 vs. 44.2。在非糖尿病志愿者中为2.9%)，而在NIDDM受试者中，全身乳酸外观转化为葡萄糖的比例增加（48.3% +-）。3.8 vs. 34.2。非糖尿病志愿者3.8%,P < 0.025)；后者提高肝脏效率约占0.33%。增加的乳酸转化为葡萄糖的40%在NIDDM和非糖尿病志愿者中，前臂和全身肌肉乳酸和丙氨酸的释放没有显著差异。因此，我们得出结论，底物向肝脏的输送增加和肝内底物向葡萄糖转化效率的提高都是NIDDM糖异生增加的重要因素，而肌肉以外的组织负责糖异生前体向肝脏的输送增加。
To assess the mechanisms responsible for increased gluconeogenesis in a 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 to glucose were also both significantly greater in diabetic subjects (18.2 .+-. 0.9 and 5.8 .+-. 0.4 .mu.mol/kg/min, respectively) than in the nondiabetic volunteers (12.6 .+-. 0.7 and 4.2 .+-. 0.3 .mu.mol/kg/min, respectively, P < 0.001 and P < 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 .mu.mole/kg/min, respectively) than in nondiabetic volunteers (4.2 .+-. 0.4 and 1.8 .+-. 0.1 .mu.mol/kg/min, respectively, P < 0.001 and P < 0.025). The proportion of systemic alanine appearance converted to glucose was 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 < 0.025); the latter increased hepatic efficiency accounted for .apprx. 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.