Lactate is a possible mediator of the glucose effect on platelet inhibition

Abstract

Glucose has been found to impair the inhibition of platelets with aspirin and alter the basal activity of nitric oxide synthase (NOS) in platelets. The aim of this work was to study the effects of glucose on the inhibitory pathways in activated platelets. A short-term incubation of glucose impaired the inhibition of platelet aggregation induced by agents activating an NOS-dependent pathway, such as l-arginine, adenosine and α-tocopherol. However, glucose had no effect on the inhibition induced by iloprost and BW245C, agents that activate the cyclic adenosine monophosphate (cAMP) signaling pathway. Potassium lactate attenuated the effects of the same inhibitors as glucose did. The inhibitors of glucose transport prevented the effect of glucose. Dichloroacetate, known to prevent the conversion of pyruvate to lactate and to decrease lactate in platelets, significantly attenuated the effect of glucose in platelets. The data support the suggestion that the effect of glucose on the inhibition of platelets by agents activating an NOS-dependent pathway is mediated by glucose metabolite lactate.

Bioenergetic profiling of platelet mitochondria during storage: 4°C storage extends platelet mitochondrial function and viability

“…PLTs metabolize glucose and produce lactate and free hydrogen ions through the glycolytic pathway, as well as carbon dioxide and water, when buffered by endogenous bicarbonate in plasma . Studies indicate that loss of PLT viability is highly correlated with increased lactate levels in combination with pH changes and decreases in glucose levels .…”

Effects of Intercept pathogen reduction treatment on extended cold storage of apheresis platelets

“…PLTs metabolize glucose and produce lactate and free hydrogen ions through the glycolytic pathway, as well as carbon dioxide and water, when buffered by endogenous bicarbonate in plasma. 29 Studies indicate that loss of PLT viability is highly correlated with increased lactate levels in combination with pH changes and decreases in glucose levels. 30,31 PLT storage in PAS has been shown to mitigate lesions caused by both cold storage and PRT.…”

Platelet mitochondria: the mighty few

“…Initially, postactivation, there is a short-lived but sharp rise in cellular oxygen consumption, which rapidly declines before platelets reach full activation, and while they are still consuming ATP. This is a highly coordinated process, achieved by blocking pyruvate from oxidization in the TCA cycle, leading to a decline in mitochondrial respiration and an accompanying rise in lactic acid [2,28 ▪▪ ,29]. The metabolic checkpoint, which determines whether glucose will be catabolized to lactate is the enzymatic activity of pyruvate kinase, which generates pyruvate and the enzyme pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA [30].…”