Acute, short-term hyperglycemia enhances shear stress-induced platelet activation in patients with type II diabetes mellitus

Gresele, Paolo; Guglielmini, Giuseppe; Angelis, Massimiliano De; Ciferri, Silvia; Ciofetta, M.; Falcinelli, Emanuela; Lalli, Carlo; Ciabattoni, Giovanni; Davı̀, Giovanni; Bolli, Geremia B.

doi:10.1016/s0735-1097(02)02972-8

Cited by 240 publications

(163 citation statements)

References 37 publications

Supporting

Mentioning

139

Contrasting

Unclassified

Order By: Relevance

“…It was, however, highest in women who were both diabetic and pregnant [41]. This increase in neutrophil activation is consistent with previous reports [42] and may contribute to pathogenesis of vascular damage and congenital malformation in the pregnancies of diabetic women [43].…”

Section: Discussionsupporting

confidence: 92%

Oxidant release is dramatically increased by elevated glucose concentrations in neutrophils from pregnant women

Petty

Kindzelskii

Chaiworapongsa

et al. 2005

The Journal of Maternal-Fetal & Neonatal Medicine

View full text Add to dashboard Cite

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 nonpregnant 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.

show abstract

Section: Discussionsupporting

confidence: 92%

Oxidant release is dramatically increased by elevated glucose concentrations in neutrophils from pregnant women

Petty

Kindzelskii

Chaiworapongsa

et al. 2005

The Journal of Maternal-Fetal & Neonatal Medicine

View full text Add to dashboard Cite

show abstract

“…This is the first study comparing male versus female bleeding time in patients with type 2 diabetes. However, the overall bleeding time data are similar to the literature (43,44). The absence of significant differences in males and females in Lp(a) concentrations suggest that the longer pretreatment bleeding time seen in females is due to a stronger effect of Lp(a) than in males ( Table 3).…”

Section: Discussionsupporting

confidence: 79%

The Mechanism by Which Flaxseed Oil Consumption Increases Bleeding Time in Patients with Type 2 Diabetes in Cape Breton, Nova Scotia, Canada is Independent of Lipoprotein(a) Concentration

et al. 2005

View full text Add to dashboard Cite

Platelet hyper-aggregation is a serious manifestation of type 2 diabetes and a precipitating factor in the most frequent cause of death in patients with type 2 diabetesmyocardial infarction. Consumption of flaxseed oil as a dietary supplement containing alphalinolenic acid (ALA, 18:3 n-3) through its metabolism to eicosapentaenoic acid (EPA, 20:5 n-3) and subsequent production of antiaggregatory eicosanoids may reduce such aggregation in vivo. Lipoprotein(a) (Lp (a)) may also influence platelet aggregation in vivo. Furthermore, serum Lp(a) concentrations are increased and bleeding time is decreased in patients with type 2 diabetes, presenting an enhanced risk of myocardial infarction. It was hypothesized that Lp(a) and bleeding time would be correlated due to the considerable molecular homology between apolipoprotein(a) and plasminogen, which should decrease bleeding time. Bleeding time is an excellent measure of in vivo platelet aggregability. The purpose of this study was to determine, if as the result of flaxseed oil consumption, Lp(a) influences the mechanism of any change in bleeding time. A secondary purpose was to determine if gender differences exist in the response of bleeding time to Lp(a) in flaxseed oil consumers. Subjects (n = 40) were randomized to treatment with flaxseed oil (n = 20) or a safflower oil placebo (n = 20). Each of groups contained equal numbers of males (n = 10) and females (n= 10). Some subjects dropped from the study due to reasons not related to treatment side effects. Subjects came for three visits, each three months apart. On each visit, age, gender, and BMI were recorded, bleeding time was performed, and serum Lp(a) concentrations were determined. At the completion of visit 2, subjects were randomized to 1 g of oil per 10 kg body weight each day for three months. Compared with pretreatment measurements, there was a statistically significant increase in bleeding time in the flaxseed oil group among both males and females posttreatment. In contrast, there was no change in the safflower group regardless of gender. Males had a statistically shorter bleeding time pretreatment while males and females showed no difference posttreatment with flaxseed oil consumption. Pretreatment values for Lp(a) and bleeding time showed a nonsignificant correlation among males and a statistically significant correlation among females. A statistically significant correlation also held when all males and females in the study were combined though at a lower value than in females. Significant correlations were lost and/or maintained upon administration of flaxseed oil and safflower oil, respectively. It is also concluded that serum Lp(a) concentrations remain unchanged following flaxseed oil consumption; thus, at least in part

show abstract

“…Thus, it is likely that poor glycaemic control is in itself an important factor in the impaired βAR-mediated NO generation seen in Type 2 diabetic patients. Hyperglycaemia has previously been associated with enhanced platelet activation [26], platelet-dependent thrombosis [27] and increased platelet generation of reactive oxygen species [28], all effects which would be consistent with a decrease in platelet-derived NO production. Other factors present in Type 2 diabetes mellitus, such as obesity, insulin resistance and alterations in lipid metabolism, could also affect NO-dependent platelet function, but we did not investigate these factors.…”

Section: Discussionmentioning

confidence: 78%

Nitric oxide generation mediated by ?-adrenoceptors is impaired in platelets from patients with Type 2 diabetes mellitus

Queen

Goubareva

et al. 2003

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis. Type 2 diabetic patients have been shown to have reduced basal platelet nitric oxide synthase activity, which is a possible contributor to the vascular complications seen in the disease. We investigated platelet nitric oxide generation stimulated by β-adrenoceptors and adenylyl cyclase in Type 2 diabetic patients and control subjects. Methods. Platelets isolated from blood taken from nine Type 2 diabetic patients and nine healthy control subjects of similar age were treated with isoproterenol 1 µmol/l, forskolin 1 µmol/l or vehicle. Platelet nitric oxide synthase activity was measured by L-[ 3 H]-arginine to L-[ 3 H]-citrulline conversion, cyclic GMP content by radioimmunoassay, and nitric oxide synthase type 3 expression by western blotting. Results. Basal platelet nitric oxide synthase activity was lower in diabetic patients than in control subjects (0.01±0.02 pmol L-citrulline/10 8 platelets, compared with 0.12±0.05; p<0.05), although no corresponding difference was seen in basal platelet cyclic GMP (0.61±0.39 and 0.13±0.22 pmol cyclic GMP/10 8 platelets respectively; p=0.37). In control subjects isoproterenol 1 µmol/l and forskolin 1 µmol/l increased platelet nitric oxide synthase activity (to 0.27±0.08 and 0.27±0.07 pmol L-citrulline/10 8 platelets respectively; p<0.05 for each in comparison with basal) and cyclic GMP (to 1.84±0.41 and 1.86±0.48; p<0.05 for each in comparison with basal). This effect was not achieved in diabetic patients. Isoproterenol-and forskolin-stimulated cyclic GMP correlated inversely with plasma glucose and HbA 1c . Platelet nitric oxide synthase type 3 expression was not different in control and diabetic subjects and was not changed by acute exposure of platelets to isoproterenol. Conclusions/interpretation. Nitric oxide generation stimulated by β-adrenoceptors and adenylyl cyclase is impaired in platelets of people with Type 2 diabetes mellitus, with no corresponding change in nitric oxide synthase type 3 expression. It is possible that this impairment contributes to the thrombotic and atherosclerotic complications of Type 2 diabetes. [Diabetologia (2003[Diabetologia ( ) 46:1474[Diabetologia ( -1482

show abstract

Acute, short-term hyperglycemia enhances shear stress-induced platelet activation in patients with type II diabetes mellitus

Cited by 240 publications

References 37 publications

Oxidant release is dramatically increased by elevated glucose concentrations in neutrophils from pregnant women

Oxidant release is dramatically increased by elevated glucose concentrations in neutrophils from pregnant women

The Mechanism by Which Flaxseed Oil Consumption Increases Bleeding Time in Patients with Type 2 Diabetes in Cape Breton, Nova Scotia, Canada is Independent of Lipoprotein(a) Concentration

Nitric oxide generation mediated by ?-adrenoceptors is impaired in platelets from patients with Type 2 diabetes mellitus

Contact Info

Product

Resources

About