Consoli A, Nurjhan N, Capani F, Gerich J
Department of Medicine, University of Pittsburgh, School of Medicine, Pennsylvania.
Diabetes. 1989 May;38(5):550-7. doi: 10.2337/diab.38.5.550.
Excessive hepatic glucose output is an important factor in the fasting hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM). To determine the relative contributions of gluconeogenesis and glycogenolysis in a quantitative manner, we applied a new isotopic approach, using infusions of [6-3H]glucose and [2-14C]acetate to trace overall hepatic glucose output and phosphoenolpyruvate gluconeogenesis in 14 postabsorptive NIDDM subjects and in 9 nondiabetic volunteers of similar age and weight. Overall hepatic glucose output was increased nearly twofold in the NIDDM subjects (22.7 +/- 1.0 vs. 12.0 +/- 0.6 mumol.kg-1.min-1 in the nondiabetic volunteers, P less than .001); phosphoenolpyruvate gluconeogenesis was increased more than threefold in the NIDDM subjects (12.7 +/- 1.4 vs. 3.6 +/- 0.4 mumol.kg-1.min-1 in the nondiabetic subjects, P less than .001) and was accompanied by increased plasma lactate, alanine, and glucagon concentrations (all P less than .05). The increased phosphoenolpyruvate gluconeogenesis accounted for 89 +/- 6% of the increase in overall hepatic glucose output in the NIDDM subjects and was significantly correlated with the fasting plasma glucose concentrations (r = .67, P less than .01). Glycogenolysis, calculated as the difference between overall hepatic glucose output and phosphoenolpyruvate gluconeogenesis, was not significantly different in the NIDDM subjects (9.9 +/- 0.06 mumol.kg-1.min-1) and the nondiabetic volunteers (8.4 +/- 0.3 mumol.kg-1.min-1). We conclude that increased gluconeogenesis is the predominant mechanism responsible for increased hepatic glucose output in NIDDM.
肝脏葡萄糖输出过多是非胰岛素依赖型糖尿病（NIDDM）空腹高血糖的一个重要因素。为了定量确定糖异生和糖原分解的相对贡献，我们应用了一种新的同位素方法，通过输注[6-³H]葡萄糖和[2-¹⁴C]乙酸盐来追踪14名吸收后NIDDM患者以及9名年龄和体重相近的非糖尿病志愿者的肝脏葡萄糖总输出量和磷酸烯醇丙酮酸糖异生情况。NIDDM患者的肝脏葡萄糖总输出量增加了近两倍（非糖尿病志愿者为12.0±0.6μmol·kg⁻¹·min⁻¹，NIDDM患者为22.7±1.0μmol·kg⁻¹·min⁻¹，P＜0.001）；NIDDM患者的磷酸烯醇丙酮酸糖异生增加了三倍多（非糖尿病患者为3.6±0.4μmol·kg⁻¹·min⁻¹，NIDDM患者为12.7±1.4μmol·kg⁻¹·min⁻¹，P＜0.001），同时伴有血浆乳酸、丙氨酸和胰高血糖素浓度升高（均P＜0.05）。在NIDDM患者中，磷酸烯醇丙酮酸糖异生增加量占肝脏葡萄糖总输出量增加量的89±6%，且与空腹血糖浓度显著相关（r = 0.67，P＜0.01）。通过计算肝脏葡萄糖总输出量与磷酸烯醇丙酮酸糖异生之间的差值得出的糖原分解量，在NIDDM患者（9.9±0.06μmol·kg⁻¹·min⁻¹）和非糖尿病志愿者（8.4±0.3μmol·kg⁻¹·min⁻¹）之间无显著差异。我们得出结论，糖异生增加是NIDDM患者肝脏葡萄糖输出增加的主要机制。
