Proinflammatory and proapoptotic effects of methylglyoxal on neutrophils from patients with type 2 diabetes mellitus.
OBJECTIVE
To determine the effect of methylglyoxal (MG) on cytokine production by, and apoptosis of, neutrophils from type 2 diabetes mellitus (T2DM) patients.


METHODS
The levels of plasma MG, cytokines released by isolated neutrophils and the apoptotic status of neutrophils were determined.


RESULTS
The higher level of plasma MG in T2DM patients was correlated positively with glycated hemoglobin levels, fasting plasma glucose levels and urine albumin/creatinine ratios. The basal levels of cytokines released from neutrophils were markedly higher in patients. MG treatment of the neutrophils isolated from diabetic patients either did not alter, or decreased, the production of cytokines. In contrast, MG induced the release of cytokines from neutrophils of non-diabetics. Moreover, the neutrophils from T2DM patients showed a greater proclivity for apoptosis, which was further increased by in vitro MG treatment.


CONCLUSIONS
MG stimulated neutrophils to release more cytokines, which might play a role in the development of infection in T2DM.
Wang
Hui
H
Department of Pharmacology, University of Saskatchewan, Saskatoon, 107 Wiggins Road, Canada S7N 5E5.
Meng
Qing H
QH
Gordon
John R
JR
Khandwala
Hasnain
H
Wu
Lingyun
L
D000368:Aged; D000419:Albuminuria / Q000652:urine; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D053148:Caspase 3 / Q000097:blood; D003401:Creatine / Q000652:urine; D016207:Cytokines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000473:pathology / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000097:blood; D011765:Pyruvaldehyde / Q000097:blood / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood