Oxygen-18 isotope of breath CO₂ linking to erythrocytes carbonic anhydrase activity: a biomarker for pre-diabetes and type 2 diabetes.

Chiranjit Ghosh,Suman Som,Chitra Selvan,Manik Pradhan,Shibendu Ghosh,Gourab D Banik,Abhijit Maity,Arpita Chakraborty,Subhankar Chowdhury

doi:10.1038/srep08137

Abstract

Carbonic anhydrase (CA), a well-characterized metalloenzyme, is associated with oxygen-18 ( 18O)-isotopic fractionations of CO2. To investigate how CA activity links the 18O of breath CO2 to pre-diabetes (PD) and type 2 diabetes (T2D) during metabolism, we studied pre- and post-dose CA activities in erythrocytes with simultaneous monitoring of 18O/ 16O-isotope ratios of breath CO2 and thereafter elucidated potential metabolic pathways underlying CA alteration in the pathogenesis of T2D. Here we show that the post-dose CA activity in both T2D and PD was markedly enhanced, whereas the non-diabetic controls (NDC) exhibited a considerable reduction in post-dose CA activity when compared with their basal CA activities. However, T2D and PD exhibited isotopic enrichments of 18O in breath CO2, while a marked depletion of 18O in CO2 was manifested in NDC. Thus, the isotopic enrichments and depletions of 18O in breath CO2 were well correlated with the changes in CA activities for controls, PD and T2D. Our findings suggest the changes in CA activities in erythrocytes may contribute to the pathogenesis of T2D and the breath C 18O 16O regulated by the CA activity as a potential biomarker for non-invasive assessment of T2D, and thus may open a new method for treating T2D.

Highlights

Correspondence and requests for materials should be addressed to Oxygen-18 isotope of breath CO2 linking to erythrocytes carbonic anhydrase activity: a biomarker for pre-diabetes and type 2 diabetes
To investigate how Carbonic anhydrase (CA) activity links the 18O of breath CO2 to pre-diabetes (PD) and type 2 diabetes (T2D) during metabolism, we studied pre- and post-dose CA activities in erythrocytes with simultaneous monitoring of 18O/ 16O-isotope ratios of breath CO2 and thereafter elucidated potential metabolic pathways underlying CA alteration in the pathogenesis of T2D
Unravelling the exact metabolic pathways involved in causing the isotopic changes of 12C 16O 18O/12C 16O 16O in breath influenced by the enzymatic activity of CA in erythrocytes remains a challenge, whenever an individual is at high-risk for altered insulin action or for the acute onset of T2D

Summary

Correspondence and requests for materials should be addressed to

Oxygen-18 isotope of breath CO2 linking to erythrocytes carbonic anhydrase activity: a biomarker for pre-diabetes and type 2 diabetes. Isotope of body water (H2 18O) are rapidly exchanged during the respiration process in humans, catalyzed by carbonic anhydrase This efficient exchange suggests the possibility of exploiting the oxygen-isotope fractionations of CO2 in exhaled breath for non-invasive assessment of early-stage pre-diabetes prior to the onset of T2D. We first investigated whether the total enzymatic activity of CA in erythrocytes is altered when individuals are in pre-diabetic and T2D states, and subsequently we assessed the precise role of CA activity in www.nature.com/scientificreports erythrocytes in response to glucose-stimulated insulin secretion that might influence the change in oxygen-isotope fractionations of CO2 in exhaled breath. We further explored the potential metabolic pathways underlying CA alteration in the pathogenesis of T2D and the mechanisms linking breath oxygen-isotopes to pre-diabetes (PD) and T2D

Results and Discussion

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