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.

Naoyuki Kawagoe,Yoshihisa Urita,Osamu Kano,Masaaki Takayanagi,Sho Kijima,Hideki Tanaka,Jonathan M Peterson

doi:10.1371/journal.pone.0160177

Naoyuki Kawagoe, Yoshihisa Urita + Show 5 more

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https://doi.org/10.1371/journal.pone.0160177

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Journal: PloS one	Publication Date: Aug 2, 2016
Citations: 10	License type: CC BY 4.0

Affiliation: Toho University

Abstract

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, 3-13C]glucose, the levels of exhaled 13CO2, 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 13C-glucose. Three types of 13C-glucose breath tests were performed thrice in each period at 2-week intervals. [3-13C]glucose results in a 13C isotope at position 1 in the pyruvate molecule, which provides 13CO2. The 13C at carbons 1 and 2 of glucose is converted to 13C at carbons 2 and 1 of acetate, respectively, which produce 13CO2. Based on metabolic differences of the labeled sites, glucose metabolism was evaluated using the results of three breath tests. The increase in 13CO2 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 [2-13C]glucose was suppressed in OLETF rats at 6–12 weeks of age, but they showed higher [3-13C]glucose oxidation than control rats at 22–25 weeks of age. In the [1-13C]glucose breath test, no significant differences in the area under the curve until 180 minutes (AUC180) 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 AUC180 of [1-13C]glucose. We conclude that breath 13CO2 excretion is reduced in OLETF rats at the primary stage of prediabetes, indicating differences in glucose oxidation kinetics between OLETF and LETO rats.

Highlights

Breath tests using glucose with 13C at a specific carbon site aids in the evaluation of just one glucose metabolism pathways
The mean values of fasting plasma glucose increased with age in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, whereas no changes were observed in LETO rats during the study period (Fig 4)
Similar 13CO2 excretion curves were obtained from the three tests for LETO rats at all three ages, whereas more variation was observed for OLETF rats

Summary

Introduction

Breath tests using glucose with 13C at a specific carbon site aids in the evaluation of just one glucose metabolism pathways. When glucose labeled at three carbon sites ([1-13C], [2-13C], and [3-13C]glucose) is used in an individual, almost all pathways can be evaluated noninvasively. The glucose clamp test is the gold standard for evaluating various aspects of glucose metabolism, including insulin resistance. It is not possible to perform invasive and labor-intensive insulin clamp tests on prediabetes patients, because there are more than 30 million such patients in the US alone. The 75-g oral glucose tolerance test is widely used in clinical practice, it poses an inevitable risk of hyperglycemia [1]. The use of a noninvasive and safe method for the management of impaired glucose metabolism is desirable, especially in longitudinal studies

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