Effect of Chronic Ethanol Consumption on Exogenous Glucose Metabolism in Rats Using [1-13C], [2-13C], and [3-13C]glucose Breath Tests.

Abstract

The C3 carbon of glucose molecules becomes the C1 carbon of pyruvate molecules during glycolysis, and the C1 and C2 carbons of glucose molecules are metabolized in the tricarboxylic acid (TCA) cycle. Utilizing this position-dependent metabolism of C atoms in glucose molecules, [1-¹³C], [2-¹³C], and [3-¹³C]glucose breath tests are used to evaluate glucose metabolism. However, the effects of chronic ethanol consumption remain incompletely understood. Therefore, we evaluated glucose metabolism in ethanol-fed rats using [1-¹³C], [2-¹³C], and [3-¹³C]glucose breath tests. Ethanol-fed (ERs) and control rats (CRs) (n = 8 each) were used in this study, and ERs were prepared by replacing drinking water with a 16% ethanol solution. We administered 100 mg/kg of [1-¹³C], [2-¹³C], or [3-¹³C]glucose to rats and collected expired air (at 10-min intervals for 180 min). We compared the ¹³CO₂ levels (Δ¹³CO₂, ‰) of breath measured by IR isotope ratio spectrometry and area under the curve (AUC) values of the ¹³CO₂ levels-time curve between ERs and CRs. ¹³CO₂ levels and AUCs after administration of [1-¹³C]glucose and [2-¹³C]glucose were lower in ERs than in CRs. Conversely, the AUC for the [3-¹³C]glucose breath test showed no significant differences between ERs and CRs, although ¹³CO₂ levels during the 110-120 min interval were significantly high in ERs. These findings indicate that chronic ethanol consumption diminishes glucose oxidation without concomitantly reducing glycolysis. Our study demonstrates the utility of ¹³C-labeled glucose breath tests as noninvasive and repeatable methods for evaluating glucose metabolism in various subjects, including those with alcoholism or diabetes.