Decreased ADP-ribosyl cyclase activity in peripheral blood mononuclear cells from diabetic patients with nephropathy.
OBJECTIVE
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 (NGD(+)) into cyclic GDP-ribose.


RESULTS
ADPRCA negatively correlated with the level of HbA1c (P = .040, R(2) = .073), 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 = .0198) and diabetes (P = .0332). 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.


CONCLUSIONS
Decreased ADPRCA significantly correlated with diabetic nephropathy. ADPRCA in PBMCs would be an important marker associated with diabetic nephropathy.
Ohtsuji
Michio
M
Division of Endocrinology and Diabetology, Kanazawa University Graduate School of Medicine, 13-1 Takaramachi, Kanazawa 920 8640, Japan.
Yagi
Kunimasa
K
Shintaku-Kubota
Miyuki
M
Kojima-Koba
Yukiko
Y
Ito
Naoko
N
Sugihara
Masako
M
Yamaaki
Naoto
N
Chujo
Daisuke
D
Nohara
Atsushi
A
Takeda
Yoshiyu
Y
Kobayashi
Junji
J
Yamagishi
Masakazu
M
Higashida
Haruhiro
H
D036541:ADP-ribosyl Cyclase / Q000097:blood*; D051997:ADP-ribosyl Cyclase 1 / Q000502:physiology; D003928:Diabetic Nephropathies / Q000201:enzymology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D006442:Glycated Hemoglobin; D008562:Membrane Glycoproteins; C517652:hemoglobin A1c protein, human; C498154:CD38 protein, human