Open AccessInvestigation 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
Author(s) -
Naoyuki Kawagoe,
Osamu Kano,
Sho Kijima,
Hideki Tanaka,
Masayoshi Takayanagi,
Yoshihisa Urita
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0160177
Subject(s) - medicine , endocrinology , carbohydrate metabolism , metabolism , diabetes mellitus , chemistry
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- 13 C]glucose, the levels of exhaled 13 CO 2 , 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 13 C-glucose. Three types of 13 C-glucose breath tests were performed thrice in each period at 2-week intervals. [3- 13 C]glucose results in a 13 C isotope at position 1 in the pyruvate molecule, which provides 13 CO 2 . The 13 C at carbons 1 and 2 of glucose is converted to 13 C at carbons 2 and 1 of acetate, respectively, which produce 13 CO 2 . Based on metabolic differences of the labeled sites, glucose metabolism was evaluated using the results of three breath tests. The increase in 13 CO 2 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- 13 C]glucose was suppressed in OLETF rats at 6–12 weeks of age, but they showed higher [3- 13 C]glucose oxidation than control rats at 22–25 weeks of age. In the [1- 13 C]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- 13 C]glucose. We conclude that breath 13 CO 2 excretion is reduced in OLETF rats at the primary stage of prediabetes, indicating differences in glucose oxidation kinetics between OLETF and LETO rats.