title: Targeting erythrocyte carbonic anhydrase and18O-isotope of breath CO2for sorting out type 1 and type 2 diabetes.
abstract: The inability to envisage the acute onset and progression of type 1 diabetes (T1D) has been a major clinical stumbling block and an important area of biomedical research over the last few decades. Therefore there is a pressing need to develop a new and an effective strategy for early detection of T1D and to precisely distinguish T1D from type 2 diabetes (T2D). Here we describe the precise role of the enzymatic activity of carbonic anhydrase (CA) in erythrocytes in the pathogenesis of T1D and T2D. We show that CA activities are markedly altered during metabolism of T1D and T2D and this facilitates to the oxygen-18 (18O) isotopic fractionations of breath CO2. In our observations, T1D exhibited considerable depletions of18O-isotopes of CO2,whereas T2D manifested isotopic enrichments of18O in breath CO2, thus unveiling a missing link of breath18O-isotopic fractionations in T1D and T2D. Our findings suggest that the alterations in erythrocytes CA activities may be the initial step of altered metabolism of T1D and T2D, and breath18O-isotope regulated by the CA activity is a potential diagnostic biomarker that can selectively and precisely distinguish T1D from T2D and thus may open a potential unifying strategy for treating these diseases.
authors: Department of Chemical, Biological &Macro-Molecular 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 &Macro-Molecular Sciences, S. N. Bose National Centre for Basic Sciences, Salt Lake, JD Block, Sector III, Kolkata, 700098, India.
authors: Santanu
authors: S
authors: Mandal
authors: Department of Chemical, Biological &Macro-Molecular 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 &Macro-Molecular 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 Medicine, Vivekananda Institute of Medical Sciences, 99 Sarat Bose Road, Kolkata, 700027, India.
authors: Prabuddha
authors: P
authors: Mukhopadhyay
authors: Department of Medicine, Raipur Institute of Medical Sciences, Raipur, 492006, Chhattisgarh, India.
authors: Shibendu
authors: S
authors: Ghosh
authors: Department of Chemical, Biological &Macro-Molecular Sciences, S. N. Bose National Centre for Basic Sciences, Salt Lake, JD Block, Sector III, Kolkata, 700098, India.|Thematic Unit of Excellence on Nanodevice Technology, S. N. Bose National Centre for Basic Sciences, Salt Lake, JD Block, Sector III, Kolkata, 700098, India.|Technical Research Centre, 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: D000293:Adolescent; D000328:Adult; D001944:Breath Tests; D002245:Carbon Dioxide / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis*; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis*; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007553:Isotope Labeling; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010103:Oxygen Isotopes / Q000737:chemistry; D013053:Spectrophotometry; D055815:Young Adult
chemical_list: D002245:Carbon Dioxide; D002256:Carbonic Anhydrases; D006442:Glycated Hemoglobin; D010103:Oxygen Isotopes; C000615259:Oxygen-18; C517652:hemoglobin A1c protein, human