Peroni O, Large V, Diraison F, Beylot M
Laboratoire de Physiologie Métabolique et Rénale, Faculté R. Laennec, Lyon, France.
Metabolism. 1997 Nov;46(11):1358-63. doi: 10.1016/s0026-0495(97)90244-4.
Using a 3-hour primed-continuous infusion of [3-3H]glucose and [2-13C]glycerol, we measured glucose production, gluconeogenesis from glycerol, and total gluconeogenesis (using mass isotopomer distribution analysis [MIDA] of glucose) in postabsorptive and starved normal and streptozotocin-diabetic rats. In normal rats, 48 hours of starvation increased (P < .01) the percent contribution of both gluconeogenesis from glycerol (from 14.4% +/- 1.8% to 25.5% +/- 4.0%) and total gluconeogenesis (from 52.2% +/- 3.9% to 89.8% +/- 1.3%) to glucose production, but the absolute gluconeogenic fluxes were not modified, since glucose production decreased. Diabetic rats showed increased glucose production in the postabsorptive state; this decreased with starvation and was comparable to the of controls after 48 hours of starvation. Gluconeogenesis was increased in postabsorptive diabetic rats (69.0% +/- 1.3%, P < .05 v controls). Surprisingly, this contribution of gluconeogenesis to glucose production was not found to be increased in 24-hour starved diabetic rats (64.4% +/- 2.4%). These rats had significant liver glycogen stores, but gluconeogenesis was also low (42.8% +/- 2.1%) in 48-hour starved diabetic rats deprived of glycogen stores. Moreover, in 24-hour starved diabetic rats infused with [3-13C]lactate, gluconeogenesis was 100% when determined by comparing circulating glucose and liver pyruvate enrichment, but only 47% +/- 3% when calculated from the MIDA of glucose. Therefore, MIDA is not a valid method to measure gluconeogenesis in starved diabetic rats. This was not explained by differences in the labeling of liver and kidney triose phosphates: functional nephrectomy of starved diabetic rats decreased glucose production, but gluconeogenesis calculated by the MIDA method was only 48% +/- 3.3%. We conclude that (1) diabetic rats have increased glucose production and gluconeogenesis in the postabsorptive state; (2) starvation decreases glucose production and increases the contribution of gluconeogenesis, but MIDA is not an appropriate method in this situation; and (3) the kidneys contribute to glucose production in starved diabetic rats.
通过对正常大鼠和链脲佐菌素诱导的糖尿病大鼠进行3小时的[3-³H]葡萄糖和[2-¹³C]甘油的预充-连续输注，我们测定了吸收后和饥饿状态下的葡萄糖生成、甘油的糖异生以及总糖异生（使用葡萄糖的质量同位素异构体分布分析[MIDA]）。在正常大鼠中，48小时饥饿增加了（P <.01）甘油糖异生（从14.4%±1.8%增至25.5%±4.0%）和总糖异生（从52.2%±3.9%增至89.8%±1.3%）对葡萄糖生成的贡献百分比，但由于葡萄糖生成减少，绝对糖异生通量未改变。糖尿病大鼠在吸收后状态下葡萄糖生成增加；饥饿时这种情况减少，且在饥饿48小时后与对照组相当。吸收后糖尿病大鼠的糖异生增加（69.0%±1.3%，与对照组相比P <.05）。令人惊讶的是，在饥饿24小时的糖尿病大鼠中未发现糖异生对葡萄糖生成的这种贡献增加（64.4%±2.4%）。这些大鼠有大量肝糖原储备，但在糖原储备耗尽的饥饿48小时糖尿病大鼠中糖异生也较低（42.8%±2.1%）。此外，在饥饿24小时的糖尿病大鼠中输注[3-¹³C]乳酸后，通过比较循环葡萄糖和肝丙酮酸富集度测定时糖异生为100%，但根据葡萄糖的MIDA计算时仅为47%±3%。因此，MIDA不是测量饥饿糖尿病大鼠糖异生的有效方法。这不能用肝和肾磷酸丙糖标记的差异来解释：饥饿糖尿病大鼠的功能性肾切除减少了葡萄糖生成，但通过MIDA方法计算的糖异生仅为48%±3.3%。我们得出结论：（1）糖尿病大鼠在吸收后状态下葡萄糖生成和糖异生增加；（2）饥饿减少葡萄糖生成并增加糖异生的贡献，但MIDA在此情况下不是合适的方法；（3）肾脏对饥饿糖尿病大鼠的葡萄糖生成有贡献。
