Oxidant release is dramatically increased by elevated glucose concentrations in neutrophils from pregnant women.
OBJECTIVE
To evaluate the mechanism of oxidative stress at glucose levels accompanying diabetic pregnancy. Specifically, we hypothesize that elevated glucose overwhelms hexose monophosphate shunt (HMS) down-regulation observed during pregnancy.


METHODS
Peripheral blood cells from normal healthy pregnant women were exposed to heightened glucose levels to provide an in vitro model of the effects of diabetic pregnancy. Changes in NAD(P)H, reactive oxygen species (ROS) and nitric oxide (NO) production were evaluated in single cells.


RESULTS
Altered metabolic dynamics, as judged by NAD(P)H autofluorescence of neutrophils from both pregnant and non-pregnant women, were observed during incubation with 14 mM glucose, a pathophysiologic level. In parallel, increased production of ROS and NO was observed. The ROS and NO levels attained in cells from pregnant women were greater than those observed in cells from non-pregnant women. Inhibitors of the HMS and NAD(P)H oxidase blocked these effects. These metabolic and oxidant changes required approximately one minute, suggesting that transient glucose spikes during pregnancy could trigger this response.


CONCLUSIONS
Elevated glucose levels enhance HMS activity and oxidant production in cells from pregnant women. This mechanism may be generally applicable in understanding the role of diabetes in materno-fetal health.
Petty
Howard R
HR
Department of Ophthalmology and Visual Sciences, The University of Michigan Medical School, Ann Arbor, MI, USA. hpetty@umich.edu
Kindzelskii
Andrei L
AL
Chaiworapongsa
Tinnakorn
T
Petty
Aaron R
AR
Romero
Roberto
R
D001786:Blood Glucose / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006801:Humans; D009249:NADP / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010427:Pentose Phosphate Pathway / Q000502:physiology; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D001786:Blood Glucose; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D009249:NADP; D005954:Glucosephosphate Dehydrogenase