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-(13)C]Glucose Breath Tests

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.