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肝脏自身调节:葡萄糖生成和糖异生对糖原分解增加的反应。

Hepatic autoregulation: response of glucose production and gluconeogenesis to increased glycogenolysis.

作者信息

Staehr Peter, Hother-Nielsen Ole, Beck-Nielsen Henning, Roden Michael, Stingl Harald, Holst Jens J, Jones Paul K, Chandramouli Visvanathan, Landau Bernard R

机构信息

Medical Endocrinological Department, Odense University Hospital, Odense, Denmark.

出版信息

Am J Physiol Endocrinol Metab. 2007 May;292(5):E1265-9. doi: 10.1152/ajpendo.00411.2006. Epub 2007 Jan 9.

DOI:10.1152/ajpendo.00411.2006
PMID:17213474
Abstract

The effect of increased glycogenolysis, simulated by galactose's conversion to glucose, on the contribution of gluconeogenesis (GNG) to hepatic glucose production (GP) was determined. The conversion of galactose to glucose is by the same pathway as glycogen's conversion to glucose, i.e., glucose 1-phosphate --> glucose 6-phosphate --> glucose. Healthy men (n = 7) were fasted for 44 h. At 40 h, hepatic glycogen stores were depleted. GNG then contributed approximately 90% to a GP of approximately 8 micromol.kg(-1).min(-1). Galactose, 9 g/h, was infused over the next 4 h. The contribution of GNG to GP declined from approximately 90% to 65%, i.e., by approximately 2 micromol.kg(-1).min(-1). The rate of galactose conversion to blood glucose, measured by labeling the infused galactose with [1-(2)H]galactose (n = 4), was also approximately 2 micromol.kg(-1).min(-1). The 41st h GP rose by approximately 1.5 micromol.kg(-1).min(-1) and then returned to approximately 9 micromol.kg(-1).min(-1), while plasma glucose concentration increased from approximately 4.5 to 5.3 mM, accompanied by a rise in plasma insulin concentration. Over 50% of the galactose infused was accounted for in blood glucose and hepatic glycogen formation. Thus an increase in the rate of GP via the glycogenolytic pathway resulted in a concomitant decrease in the rate of GP via GNG. While the compensatory response to the galactose administration was not complete, since GP increased, hepatic autoregulation is operative in healthy humans during prolonged fasting.

摘要

通过半乳糖转化为葡萄糖来模拟糖原分解增加对糖异生(GNG)对肝脏葡萄糖生成(GP)贡献的影响进行了测定。半乳糖转化为葡萄糖与糖原转化为葡萄糖的途径相同,即葡萄糖1-磷酸→葡萄糖6-磷酸→葡萄糖。7名健康男性禁食44小时。在40小时时,肝脏糖原储备耗尽。此时GNG对约8微摩尔·千克-1·分钟-1的GP贡献约90%。在接下来的4小时内以9克/小时的速度输注半乳糖。GNG对GP的贡献从约90%降至65%,即下降约2微摩尔·千克-1·分钟-1。通过用[1-(2)H]半乳糖标记输注的半乳糖来测量半乳糖转化为血糖的速率(n = 4),也约为2微摩尔·千克-1·分钟-1。第41小时GP上升约1.5微摩尔·千克-1·分钟-1,然后恢复到约9微摩尔·千克-1·分钟-1,同时血浆葡萄糖浓度从约4.5毫摩尔/升增加到5.3毫摩尔/升,伴随着血浆胰岛素浓度的升高。输注的半乳糖超过50%在血糖和肝糖原形成中得到体现。因此,通过糖原分解途径增加GP速率会导致通过GNG的GP速率相应降低。虽然对半乳糖给药的代偿反应不完全,因为GP增加了,但在健康人类长时间禁食期间肝脏自动调节起作用。

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