Toft I, Jenssen T
Department of Nephrology, University Hospital of Northern Norway, Tromsø.
Scand J Clin Lab Invest. 2005;65(4):307-20. doi: 10.1080/00365510510025692.
An autoregulatory mechanism involving a reciprocal relationship between gluconeogenesis and glycogenolysis regulates endogenous glucose production (EGP) in healthy individuals. In type 2 diabetes, fasting hyperglycemia may be due to increased EGP.
To examine gluconeogenesis and autoregulation of EGP in type 2 diabetes, 9 type 2 diabetics and 8 healthy controls were studied during a 3-h infusion of 30 micromol/kg/min Na-lactate. The diabetics were also studied during a control infusion of Na-bicarbonate. To standardize levels of glucoregulatory hormones, plasma insulin, growth hormone, and glucagon were clamped at identical levels during the three experiments. Glucagon levels were elevated from basal levels to approximately 330 ng/l when the lactate or bicarbonate infusions were started, in order to mimic the hyperglucagonemia often seen in diabetes. Lactate gluconeogenesis and total EGP were measured by infusions of [6-(3)H] glucose and [U-14C] lactate.
In the bicarbonate experiments, hyperglugagonemia increased lactate gluconeogenesis in the diabetic patients from 4.3+/-1.8 to 6.1+/-2.4 micromol/kg/min (p=0.04). EGP did not change significantly (basal EGP: 15.3+/-3.9, EGP at the end of the study: 14.2+/-3.9 micromol/kg/min, p=0.14). During both lactate experiments, plasma lactate increased more than 4-fold. The increase in lactate gluconeogenesis was significantly higher in diabetics than in controls (values obtained at the end of experiments minus basal values: 10.8+/-3.6 versus 6.4+/-3.6 micromol/kg/min, p=0.03). Compared with normal subjects, the diabetic patients had higher EGP values both at basal conditions (p=0.001) and during lactate infusion (p=0.005). Despite augmented gluconeogenesis, EGP did not change during lactate and glucagon infusion in any of the groups (diabetics, basal EGP: 15.4+/-2.7 versus EGP at the end of experiments: 15.6+/-3.6 micromol/kg/min, p>0.30. Controls, basal EGP: 11.8+/-0.8 versus EGP at the end of experiments: 11.6+/-1.9 micromol/kg/min, p>0.30).
Although type 2 diabetics have increased EGP and increased lactate gluconeogenesis, the hepatic autoregulation of EGP during increased substrate-induced gluconeogenesis seems to be intact.
一种涉及糖异生和糖原分解之间相互关系的自动调节机制，可调节健康个体的内源性葡萄糖生成（EGP）。在2型糖尿病中，空腹高血糖可能归因于EGP增加。
为研究2型糖尿病患者的糖异生及EGP的自动调节，对9名2型糖尿病患者和8名健康对照者进行了一项实验，在3小时内以30微摩尔/千克/分钟的速度输注乳酸钠。还对糖尿病患者进行了碳酸氢钠对照输注实验。为使血糖调节激素水平标准化，在三项实验中，将血浆胰岛素、生长激素和胰高血糖素钳制在相同水平。开始输注乳酸或碳酸氢钠时，将胰高血糖素水平从基础水平提高到约330纳克/升，以模拟糖尿病中常见的高胰高血糖素血症。通过输注[6-(3)H]葡萄糖和[U-14C]乳酸来测量乳酸糖异生和总EGP。
在碳酸氢钠实验中，高胰高血糖素血症使糖尿病患者的乳酸糖异生从4.3±1.8微摩尔/千克/分钟增加到6.1±2.4微摩尔/千克/分钟（p = 0.04）。EGP无显著变化（基础EGP：15.3±3.9，实验结束时EGP：14.2±3.9微摩尔/千克/分钟，p = 0.14）。在两项乳酸实验中，血浆乳酸增加了4倍以上。糖尿病患者乳酸糖异生的增加显著高于对照组（实验结束时的值减去基础值：10.8±3.6对6.4±3.6微摩尔/千克/分钟，p = 0.03）。与正常受试者相比，糖尿病患者在基础状态（p = 0.001）和输注乳酸期间（p = 0.005）的EGP值均较高。尽管糖异生增加，但在任何一组（糖尿病患者，基础EGP：15.4±2.7对实验结束时EGP：15.6±3.6微摩尔/千克/分钟，p>0.30。对照组，基础EGP：11.8±0.8对实验结束时EGP：11.6±1.9微摩尔/千克/分钟，p>0.30）中，输注乳酸和胰高血糖素期间EGP均无变化。
尽管2型糖尿病患者的EGP增加且乳酸糖异生增加，但在底物诱导的糖异生增加期间，肝脏对EGP的自动调节似乎是完整的。
