Objective

Fasting results in major metabolic changes including a switch from glycogenolysis to gluconeogenesis to maintain glucose homeostasis. However, the relationship between the length of fasting and the relative contribution of gluconeogenic substrates remains unclear. We investigated the relative contribution of glycogen, lactate, and glycerol in glucose production of male C57BL/6 J-albino mice after 6, 12, and 18 h of fasting.

Methods

We used non-perturbative infusions of ¹³C₃ lactate, ¹³C₃ glycerol, and ¹³C₆ glucose combined with liquid chromatography mass spectrometry and metabolic flux analysis to study the contribution of substrates in gluconeogenesis (GNG).

Results

During infusion studies, both lactate and glycerol significantly label about 60% and 30–50% glucose carbon, respectively, but glucose labels much more lactate (∼90%) than glycerol carbon (∼10%). Our analyses indicate that lactate, but not glycerol is largely recycled during all fasting periods such that lactate is the largest direct contributor to GNG via the Cori cycle but a minor source of new glucose carbon (overall contribution). In contrast, glycerol is not only a significant direct contributor to GNG but also the largest overall contributor to GNG regardless of fasting length. Prolonged fasting decreases both the whole body turnover rate of glucose and lactate but increases that of glycerol, indicating that the usage of glycerol in GNG become more significant with longer fasting.

Conclusion

Collectively, these findings suggest that glycerol is the dominant overall contributor of net glucose carbon in GNG during both short and prolonged fasting.

中文翻译：

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在短期和长期禁食期间，甘油而不是乳酸是小鼠糖异生的主要净碳源。

客观的

空腹导致主要的代谢变化，包括从糖原分解到糖异生，以维持葡萄糖稳态。然而，禁食时间和糖异生底物的相对贡献之间的关系仍然不清楚。我们调查了禁食6、12和18小时后，雄性C57BL / 6 J-白化病小鼠糖原，乳酸和甘油在葡萄糖生产中的相对贡献。

方法

我们使用¹³ C ₃乳酸，¹³ C ₃甘油和¹³ C ₆葡萄糖的无扰动输注结合液相色谱质谱和代谢通量分析来研究底物在糖异生（GNG）中的作用。

结果

在输液研究期间，乳酸和甘油均分别显着标记约60％和30-50％的葡萄糖碳，但葡萄糖标记的乳酸（约90％）比甘油碳（约10％）高得多。我们的分析表明，在所有禁食期间，乳酸（而不是甘油）在很大程度上被回收，因此，乳酸是通过Cori循环对GNG的最大直接贡献者，而新葡萄糖碳的来源极少（总体贡献）。相反，无论禁食时间长短，甘油不仅是GNG的重要直接贡献者，还是GNG的最大总体贡献者。长期禁食会降低全身葡萄糖和乳酸的周转率，但会增加甘油的周转率，这表明禁食时间越长，GNG中甘油的使用就越重要。

结论

总体而言，这些发现表明，在空腹和长期禁食期间，甘油是GNG中净葡萄糖碳的主要总体成分。