title: Oxygen-18 isotope of breath CO₂ linking to erythrocytes carbonic anhydrase activity: a biomarker for pre-diabetes and type 2 diabetes.
abstract: Carbonic anhydrase (CA), a well-characterized metalloenzyme, is associated with oxygen-18 ( (18)O)-isotopic fractionations of CO₂. To investigate how CA activity links the (18)O 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 (18)O/ (16)O-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 (18)O in breath CO₂, while a marked depletion of (18)O in CO₂ was manifested in NDC. Thus, the isotopic enrichments and depletions of (18)O 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 (18)O (16)O 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.
authors: Department of Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Salt Lake, JD Block, Sector III, Kolkata-700098, India.
authors: Chiranjit
authors: C
authors: Ghosh
authors: Department of Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Salt Lake, JD Block, Sector III, Kolkata-700098, India.
authors: Gourab D
authors: GD
authors: Banik
authors: Department of Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Salt Lake, JD Block, Sector III, Kolkata-700098, India.
authors: Abhijit
authors: A
authors: Maity
authors: Department of Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Salt Lake, JD Block, Sector III, Kolkata-700098, India.
authors: Suman
authors: S
authors: Som
authors: Department of Endocrinology, Institute of Post Graduate Medical Education &Research and S.S.K.M Hospital, 244 A.J.C Bose Road, Kolkata-700020, India.
authors: Arpita
authors: A
authors: Chakraborty
authors: Department of Endocrinology, Institute of Post Graduate Medical Education &Research and S.S.K.M Hospital, 244 A.J.C Bose Road, Kolkata-700020, India.
authors: Chitra
authors: C
authors: Selvan
authors: Department of Medicine, Vivekananda Institute of Medical Sciences, 99 Sarat Bose Road, Kolkata-700027, India.
authors: Shibendu
authors: S
authors: Ghosh
authors: Department of Endocrinology, Institute of Post Graduate Medical Education &Research and S.S.K.M Hospital, 244 A.J.C Bose Road, Kolkata-700020, India.
authors: Subhankar
authors: S
authors: Chowdhury
authors: 1] Department of Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Salt Lake, JD Block, Sector III, Kolkata-700098, India [2] Thematic Unit of Excellence on Nanodevice Technology, S. N. Bose National Centre for Basic Sciences, Salt Lake, JD Block, Sector III, Kolkata-700098, India.
authors: Manik
authors: M
authors: Pradhan
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001944:Breath Tests / Q000379:methods*; D002245:Carbon Dioxide / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis*; D004912:Erythrocytes / Q000201:enzymology*; D005215:Fasting / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D053858:Metabolic Networks and Pathways; D010103:Oxygen Isotopes; D011236:Prediabetic State / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology
chemical_list: D015415:Biomarkers; D007328:Insulin; D010103:Oxygen Isotopes; D002245:Carbon Dioxide; D002256:Carbonic Anhydrases
references: Science. 1967 Jan 6;155(3758):44-7
references: 4959309
references: Med Clin North Am. 2004 Jul;88(4):787-835, ix
references: 15308380
references: Science. 1991 Oct 25;254(5031):573-6
references: 1948033
references: Anal Chem. 2002 May 1;74(9):2003-7
references: 12033299
references: Proc Natl Acad Sci U S A. 1988 Mar;85(6):1727-31
references: 3162303
references: Anal Chem. 2011 Mar 15;83(6):2220-6
references: 21341717
references: J Breath Res. 2014 Sep;8(3):036001
references: 24946152
references: Science. 2009 May 29;324(5931):1155-6
references: 19478173
references: Science. 2001 Mar 30;291(5513):2584-7
references: 11283366
references: Nature. 2001 Dec 13;414(6865):799-806
references: 11742412
references: Nature. 2001 Dec 13;414(6865):782-7
references: 11742409
references: J Biol Chem. 1966 Nov 10;241(21):5137-49
references: 4958988
references: Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15815-20
references: 9861053
references: Clin Chim Acta. 1987 Jul 15;166(2-3):227-36
references: 3113773
references: Nature. 2006 Dec 14;444(7121):840-6
references: 17167471
references: Ann N Y Acad Sci. 1997 Sep 20;827:163-9
references: 9329751
references: Science. 1977 Jul 29;197(4302):471-2
references: 406674
references: Respir Physiol. 1992 Sep;89(3):319-27
references: 1410845
references: Biochem Genet. 2007 Jun;45(5-6):431-9
references: 17464559
references: Biochem Int. 1991 Mar;23(4):779-89
references: 1908243
references: Annu Rev Physiol. 1996;58:523-38
references: 8815807
references: Science. 2005 Jan 21;307(5708):384-7
references: 15662004