Increased intracellular calcium and altered phorbol dibutyrate binding to intact platelets in young subjects with insulin-dependent and non—insulin-dependent diabetes mellitus

Takaya, Junji; Iwamoto, Y.; Higashino, Hirohiko; Ishihara, Reiko; Kobayashi, Yohnosuke

doi:10.1016/s0026-0495(97)90085-8

Cited by 13 publications

(5 citation statements)

References 31 publications

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“…Platelet abnormalities in diabetes mellitus include deranged calcium homeostasis. Most of the published data are consistent in showing (i) increased platelet [Ca 2+ ] in the resting state and (ii) higher mobilization after stimulation with various agonists [1–8].…”

Section: Introductionmentioning

confidence: 68%

“…While there is evidence of abnormalities in cytosolic Ca 2+ concentrations in diabetes [1–8], very little is known about the expression of human platelet Ca 2+ ‐ATPases in this disease. Here, we report for the first time the major modulation of the expression of PMCA4b mRNA and/or protein in platelets isolated from patients with either T1D or T2D.…”

Section: Discussionmentioning

confidence: 99%

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Platelet PMCA‐ and SERCA‐type Ca2+‐ATPase expression in diabetes: a novel signature of abnormal megakaryocytopoiesis

Chaâbane

Dally

Corvazier

et al. 2007

Journal of Thrombosis and Haemostasis

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Summary. Background: Previous studies have shown platelet Ca2+ abnormalities in diabetes mellitus and some reports suggest abnormal platelet production. Platelet Ca2+ homeostasis is controlled by a multi‐Ca2+‐ATPase system that includes two plasma membrane Ca2+‐ATPase (PMCA) and seven sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA) isoforms. In addition, we recently found that the expression of PMCA4b and SERCA3 isoforms may serve as new markers of abnormal megakaryocytopoiesis [Nurden P et al. Impaired megakaryocytopoiesis in type 2B von Willebrand disease with severe thrombocytopenia. Blood 2006; 108: 2587–95]. Aim: To analyze the expression of major platelet Ca2+‐ATPases in 27 patients with type 1 or type 2 diabetes (T1D or T2D) compared with normal donors. Methods: Investigation of protein and mRNA expressions of PMCA1b and PMCA4b, and SERCA2b, SERCA3a and SERCA3b, using specific Western blotting and reverse transcriptase‐polymerase chain reaction, respectively. Results: Remarkably, all patients with T1D were found to present a higher expression of PMCA4b protein (212% ± 28%; n = 10) and PMCA4b mRNA (155% ± 16%; n = 17), coupled with a higher expression of SERCA3b mRNA (165% ± 9%) in some cases. Patients with T2D (n = 10) were also studied for protein expression and were found to present similar major upregulation of the expression of PMCA4b protein (180% ± 28%; n = 10). Lastly, five of 10 patients with T1D were studied for PMCA4b expression after insulin treatment, with four of five recovering normal expression (96% ± 15%; n = 5). Conclusions: Compared with the expression of PMCA4b upon platelet maturation, platelets from diabetic patients exhibit similarities with immature megakaryocytes. Thus, this study reinforces the idea that abnormal megakaryocytopoiesis can provide additional insights into diabetes and could represent a novel therapeutic target for antithrombotic drugs.

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Section: Introductionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Platelet PMCA‐ and SERCA‐type Ca2+‐ATPase expression in diabetes: a novel signature of abnormal megakaryocytopoiesis

Chaâbane

Dally

Corvazier

et al. 2007

Journal of Thrombosis and Haemostasis

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“…Cord blood samples were collected by the Labor Ward staff and kept at 4°C. Platelets were isolated as previously described (13). Approximately 10 mL of cord blood was drawn into 3.8% (wt/vol) acid citrate buffer (10:1, vol/vol) and was centrifuged at 200 g for 10 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Intracellular Magnesium and Adipokines in Umbilical Cord Plasma and Infant Birth Size

et al. 2007

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Many epidemiologic studies have disclosed that restricted fetal growth has been associated with an increased risk of insulin resistance in adulthood. We studied the relationship of intracellular magnesium ([Mg 2ϩ ] i ) in cord blood platelets to adipocytokine and birth size. The subjects were 20 infants with small for gestational age (SGA) and 45 infants with appropriate for gestational age (AGA). By using a fluorescent probe, we examined [Mg 2ϩ ] i of platelets in the cord blood. Cord plasma insulin, IGF-I, ghrelin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), and leptin levels were determined with the use of ELISA. Mean [Mg 2ϩ ] i was lower in the SGA than in the AGA groups (p Ͻ 0.001). Adiponectin and IGF-I were also lower in the SGA than in the AGA, whereas PAI-1 was higher in the SGA. [Mg 2ϩ ] i was significantly correlated with birth weight, birth length, and adiponectin. Birth weight was also correlated with cord plasma IGF-I, adiponectin, and leptin. Quantitative insulin sensitivity check index (QUICKI) was lower in the SGA group than in the AGA group. T here is no doubt that low birth weight is associated with adult disorders characterized by insulin resistance such as type 2 diabetes, hypertension, dyslipidemia, and coronary heart disease (1,2). It has been proposed that this association results from fetal programming in response to the intrauterine environment (3). Intracellular magnesium (Mg 2ϩ ) i deficiency occurs in patients with diabetes and vascular diseases (4 -6). Taken together, these experimental and epidemiologic results suggest that the correlation between Mg 2ϩ and birth weight are important determinants of insulin resistance. We and other investigators reported that insulin could regulate intracellular Mg 2ϩ ([Mg 2ϩ ] i ) in platelets (7,8). Platelets are often used in the study of cellular cation metabolism in diseases (9), because they are readily available for study and are thought to share a number of features with vascular smooth muscle cells. Human platelets have been shown to have insulin receptors with similar characteristics as those in other cells (10 ] i and birth weight (11). As the next step, we hypothesized that [Mg 2ϩ ] i may affect metabolic hormones and insulin resistance in infants. We studied the correlation among [Mg 2ϩ ] i , adipokines in cord blood and insulin resistance index. SUBJECTS AND METHODSThe study group consisted of 65 singleton subjects with gestational ages ranging from 33 to 41 wk, and birth weights ranging from 1332 to 4030 g. Most of these subjects had been previously recruited for an observational study of [Mg 2ϩ ] i (11). Gestational age was measured by dating the last menstrual period at the time of registration. None of the subjects were treated with medications, including magnesium, and did not show any evidence of endocrine malfunction or recent use of drugs that might potentially alter electrolyte balance. All the mothers were Japanese with no remarkable past medical histories, and they manifested no abno...

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“…Enhanced calcium mobilisation has been observed in platelets from Type 1 and Type 2 diabetic patients [17, 38]. Intracellular calcium homeostasis in platelets of patients with non-insulin-dependent diabetes is altered, leading to increased adhesiveness and spontaneous aggregation [39].…”

Section: Discussionmentioning

confidence: 99%

Exacerbation of Glycoprotein VI-Dependent Platelet Responses in a Rhesus Monkey Model of Type 1 Diabetes

Arthur

Shen

Chen

et al. 2013

Journal of Diabetes Research

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Thrombosis is a life-threatening complication of diabetes. Platelet reactivity is crucial to thrombus formation, particularly in arterial vessels and in thrombotic complications causing myocardial infarction or ischaemic stroke, but diabetic patients often respond poorly to current antiplatelet medication. In this study, we used a nonhuman primate model of Type 1 diabetes to measure early downstream signalling events following engagement of the major platelet collagen receptor, glycoprotein (GP)VI. Diabetic monkeys were given enough insulin to maintain their blood glucose levels either at ~8 mM (well-controlled diabetes) or ~15 mM (poorly controlled diabetes). Flow cytometric analysis was used to measure platelet reactive oxygen species (ROS) generation, calcium mobilisation, receptor surface expression, and immature platelet fraction. We observed exacerbated intracellular ROS and calcium flux associated with engagement of GPVI in monkeys with poorly controlled diabetes. GPVI surface levels did not differ between healthy monkeys or the two diabetic groups. Treatment of platelets with the specific Syk inhibitor BAY61-3606 inhibited GPVI-dependent ROS and, importantly, reduced ROS generation in the poorly controlled diabetes group to that observed in healthy monkeys. These data indicate that glycaemic control is important in reducing GPVI-dependent platelet hyperreactivity and point to a potential antithrombotic therapeutic benefit of Syk inhibition in hyperglycaemic diabetes.

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Increased intracellular calcium and altered phorbol dibutyrate binding to intact platelets in young subjects with insulin-dependent and non—insulin-dependent diabetes mellitus

Cited by 13 publications

References 31 publications

Platelet PMCA‐ and SERCA‐type Ca2+‐ATPase expression in diabetes: a novel signature of abnormal megakaryocytopoiesis

Platelet PMCA‐ and SERCA‐type Ca2+‐ATPase expression in diabetes: a novel signature of abnormal megakaryocytopoiesis

Intracellular Magnesium and Adipokines in Umbilical Cord Plasma and Infant Birth Size

Exacerbation of Glycoprotein VI-Dependent Platelet Responses in a Rhesus Monkey Model of Type 1 Diabetes

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