Investigation of Metabolism of Exogenous Glucose at the Early Stage and Onset of Diabetes Mellitus in Otsuka Long-Evans Tokushima Fatty Rats Using [1, 2, 3-13C] Glucose Breath Tests
Investigation of Metabolism of Exogenous Glucose at the Early Stage and Onset of Diabetes Mellitus in Otsuka Long-Evans Tokushima Fatty Rats Using [1, 2, 3-13C] Glucose Breath Tests
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DOI：
10.1371/journal.pone.0160177
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发表时间：
2016-08-02
期刊：
影响因子：
3.7
通讯作者：
Urita, Yoshihisa
中科院分区：
文献类型：
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作者：
Kawagoe, Naoyuki;Kano, Osamu;Urita, Yoshihisa
本研究旨在评价大冢长万德岛肥胖症(OLETF)大鼠糖尿病早期和发病过程中糖代谢的变化。具体来说，在口服[1，2，3-C-13]葡萄糖后，测量呼出的(CO2)-C-13的水平，这种呼气最有可能来自丙酮酸脱羧基和三羧酸。8只OLETF大鼠和8只对照大鼠(Long-Evans Tokushima Otsuka[Leto])注射C-13-葡萄糖。每隔2周进行三次C-13-葡萄糖呼气试验。[3-C-13]葡萄糖在丙酮酸分子的第一位产生C-13同位素，提供(CO2)-C-13。葡萄糖的碳1和碳2上的C-13分别在乙酸酯的碳2和碳1上转化为C-13，生成(CO2)-C-13。根据标记部位的代谢差异，使用三种呼气试验的结果来评估葡萄糖代谢。在三种呼气试验中，OLETF大鼠的(CO2)-C-13排泄量的增加均延迟于对照组，提示OLETF大鼠的糖代谢低于对照组。此外，两组患者的整体糖代谢均随年龄增长而增加。OLETF大鼠在6-12周龄时对[2-C-13]葡萄糖的利用受到抑制，但在22-25周龄时表现出较高的[3-C-13]葡萄糖氧化能力。在[1-C-13]葡萄糖呼气试验中，任何年龄的OLETF和LETO大鼠之间的曲线下面积(AUC(180))均无显著差异。不同年龄组和两组大鼠的葡萄糖代谢动力学不同；然而，基于[1-C-13]葡萄糖的总体AUC(180)，这些差异并不显著。我们的结论是，在糖尿病前期，OLETF大鼠的呼吸(CO2)-C-13排泄减少，这表明OLETF和LETO大鼠的葡萄糖氧化动力学存在差异。
This study aimed to evaluate changes in glucose metabolism at the early stage and onset of diabetes in Otsuka Long-Evans Tokushima Fatty ( OLETF) rats. Specifically, after the oral administration of [1, 2, 3-C-13] glucose, the levels of exhaled (CO2)-C-13, which most likely originated from pyruvate decarboxylation and tricarboxylic acid, were measured. Eight OLETF rats and eight control rats ( Long-Evans Tokushima Otsuka [LETO]) were administered C-13-glucose. Three types of C-13-glucose breath tests were performed thrice in each period at 2-week intervals. [3-C-13] glucose results in a C-13 isotope at position 1 in the pyruvate molecule, which provides (CO2)-C-13. The C-13 at carbons 1 and 2 of glucose is converted to C-13 at carbons 2 and 1 of acetate, respectively, which produce (CO2)-C-13. Based on metabolic differences of the labeled sites, glucose metabolism was evaluated using the results of three breath tests. The increase in (CO2)-C-13 excretion in OLETF rats was delayed in all three breath tests compared to that in control rats, suggesting that OLETF rats had a lower glucose metabolism than control rats. In addition, overall glucose metabolism increased with age in both groups. The utilization of [2-C-13] glucose was suppressed in OLETF rats at 6-12 weeks of age, but they showed higher [3-C-13] glucose oxidation than control rats at 22-25 weeks of age. In the [1-C-13] glucose breath test, no significant differences in the area under the curve until 180 minutes (AUC(180)) were observed between OLETF and LETO rats of any age. Glucose metabolism kinetics were different between the age groups and two groups of rats; however, these differences were not significant based on the overall AUC(180) of [1-C-13] glucose. We conclude that breath (CO2)-C-13 excretion is reduced in OLETF rats at the primary stage of prediabetes, indicating differences in glucose oxidation kinetics between OLETF and LETO rats.