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Experimental Diabetes Research
Volume 2008 (2008), Article ID 897508, 8 pages
http://dx.doi.org/10.1155/2008/897508
Research Article

Decreased ADP-Ribosyl Cyclase Activity in Peripheral Blood Mononuclear Cells from Diabetic Patients with Nephropathy

1Division of Endocrinology and Diabetology, Kanazawa University Graduate School of Medicine, 13-1 Takaramachi, Kanazawa 920 8640, Japan
2Division of Cardiovascular Medicine, Department of Internal Medicine, Kanazawa University Graduate School of Medicine, 13-1 Takaramachi, Kanazawa 920 8640, Japan
3Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, 13-1 Takaramachi, Kanazawa 920 8640, Japan

Received 30 September 2008; Accepted 12 December 2008

Academic Editor: Andreas Pfützner

Copyright © 2008 Michio Ohtsuji et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Aims/hypothesis. ADP-ribosyl-cyclase activity (ADPRCA) of CD38 and other ectoenzymes mainly generate cyclic adenosine 5'diphosphate-(ADP-) ribose (cADPR) as a second messenger in various mammalian cells, including pancreatic beta cells and peripheral blood mononuclear cells (PBMCs). Since PBMCs contribute to the pathogenesis of diabetic nephropathy, ADPRCA of PBMCs could serve as a clinical prognostic marker for diabetic nephropathy. This study aimed to investigate the connection between ADPRCA in PBMCs and diabetic complications. Methods. PBMCs from 60 diabetic patients (10 for type 1 and 50 for type 2) and 15 nondiabetic controls were fluorometrically measured for ADPRCA based on the conversion of nicotinamide guanine dinucleotide ( N G D + ) into cyclic GDP-ribose. Results. ADPRCA negatively correlated with the level of HbA1c ( 𝑃 = . 0 4 0 , 𝑅 2 = . 0 7 3 ), although ADPRCA showed no significant correlation with gender, age, BMI, blood pressure, level of fasting plasma glucose and lipid levels, as well as type, duration, or medication of diabetes. Interestingly, patients with nephropathy, but not other complications, presented significantly lower ADPRCA than those without nephropathy ( 𝑃 = . 0 1 9 8 ) and diabetes ( 𝑃 = . 0 3 3 2 ). ANCOVA analysis adjusted for HbA1c showed no significant correlation between ADPRCA and nephropathy. However, logistic regression analyses revealed that determinants for nephropathy were systolic blood pressure and ADPRCA, not HbA1c. Conclusion/interpretation. Decreased ADPRCA significantly correlated with diabetic nephropathy. ADPRCA in PBMCs would be an important marker associated with diabetic nephropathy.