title: Decreased ADP-ribosyl cyclase activity in peripheral blood mononuclear cells from diabetic patients with nephropathy.
abstract: 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.
authors.affiliation: Division of Endocrinology and Diabetology, Kanazawa University Graduate School of Medicine, 13-1 Takaramachi, Kanazawa 920 8640, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Ohtsuji
authors.forename: Kunimasa
authors.initials: K
authors.lastname: Yagi
authors.forename: Miyuki
authors.initials: M
authors.lastname: Shintaku-Kubota
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kojima-Koba
authors.forename: Naoko
authors.initials: N
authors.lastname: Ito
authors.forename: Masako
authors.initials: M
authors.lastname: Sugihara
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamaaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Chujo
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nohara
authors.forename: Yoshiyu
authors.initials: Y
authors.lastname: Takeda
authors.forename: Junji
authors.initials: J
authors.lastname: Kobayashi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamagishi
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Higashida
mesh_terms: 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
chemical_list: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D006442:Glycated Hemoglobin; D008562:Membrane Glycoproteins; C517652:hemoglobin A1c protein, human; C498154:CD38 protein, human