Alterations in insulin-signaling and coagulation pathways in platelets during hyperglycemia-hyperinsulinemia in healthy non-diabetic subject.
Alterations in insulin-signaling and coagulation pathways in platelets during hyperglycemia-hyperinsulinemia in healthy non-diabetic subject.
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DOI：
10.1016/j.thromres.2014.06.029
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发表时间：
2014-09
影响因子：
7.5
通讯作者：
Boden, Guenther
中科院分区：
文献类型：
--
作者：
Rao, A. Koneti;Freishtat, Robert J.;Jalagadugula, Gauthami;Singh, Anamika;Mao, Guangfen;Wiles, Andrew;Cheung, Peter;Boden, Guenther
关键词：
糖尿病(DM)是一种血栓前状态和促炎状态。即使没有糖尿病的患者也会出现高血糖(HG)。我们已经证明，在健康的非糖尿病受试者中，合并HG和高胰岛素血症(HI)会增加循环组织因子(TF)和凝血酶的生成。为了了解在健康非糖尿病状态下联合应用HG和HI引起的血小板和单核细胞通路的变化，我们用葡萄糖输注钳对一名健康非糖尿病受试者联合应用HG(葡萄糖∼200 mg/dL)和HI 24小时前后去白细胞的血小板和单核细胞的全基因组表达谱进行了研究。我们定义了血小板和单核细胞共有的依赖时间的差异基因表达(24小时折叠变化(FC)≥2)。独创性通路分析揭示了典型的胰岛素受体信号通路和凝血通路的变化。初步筛选出9个差异表达基因进行qRT-PCR验证。将24小时血小板样本与0小时样本加4名对照组进行比较。5个转录本在血小板中得到证实，6个在单核细胞中得到证实。在胰岛素信号通路中，血小板GSK3B和PTPN1上调，STXBP4下调，在凝血通路中F3和TFPI上调。单核细胞、PIK3C3、PTPN11和TFPI表达下调。血小板和单核细胞中的β-3、PTPN11蛋白和Tf抗原表达增加。即使在非糖尿病状态下，HG+HI持续24小时也会引起血小板和单核细胞的变化。他们建议下调胰岛素信号，上调转铁蛋白。需要进一步的研究来阐明导致糖尿病血栓前状态和炎症状态的细胞变化。
Diabetes mellitus (DM) is a prothrombotic and proinflammatory state. Hyperglycemia (HG) is encountered even in patients without DM. We have shown that combined HG and hyperinsulinemia (HI) in healthy non-diabetic subjects increased circulating tissue factor (TF) and thrombin generation. To understand the changes in platelet and monocyte pathways induced by combined HG and HI in healthy non-diabetic state, we performed whole genome expression profiling of leukocyte-depleted platelets and monocytes before and after 24 hours of combined HG (glucose ∼200 mg/dL) and HI by glucose infusion clamp in a healthy non-diabetic subject. We defined time-dependent differential mRNA expression (24 versus 0 hour fold change (FC) ≥2) common to platelets and monocytes. Ingenuity Pathways Analysis revealed alterations in canonical insulin receptor signaling and coagulation pathways. A preliminary group of 9 differentially expressed genes was selected for qRT-PCR confirmation. Platelet 24 hour sample was compared to the 0 hour sample plus 4 controls. Five transcripts in platelets and 6 in monocytes were confirmed. Platelet GSK3B and PTPN1 were upregulated, and STXBP4 was downregulated in insulin signaling, and F3 and TFPI were upregulated in coagulation pathways. Monocyte, PIK3C3, PTPN11 and TFPI were downregulated. Platelet GSKβ3 and PTPN11 protein and TF antigen in platelets and monocytes was increased. Even in non-diabetic state, HG+HI for 24 hours induces changes in platelets and monocytes. They suggest downregulation of insulin signaling and upregulation of TF. Further studies are needed to elucidate cellular alterations leading to the prothrombotic and proinflammatory state in DM.
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影响因子：
3.7
作者：
Perveen R;Funk K;Thuma J;Wulf Ridge S;Cao Y;Akkerman JW;Chen X;Akbar H
通讯作者：
Akbar H
影响因子：
2.8
作者：
Kakouros N;Rade JJ;Kourliouros A;Resar JR
通讯作者：
Resar JR
影响因子：
10.4
作者：
di Santo, A.;Amore, C.;Evangelista, V.
通讯作者：
Evangelista, V.
影响因子：
4.8
作者：
Ferreira, IA;Eybrechts, KL;Akkerman, JWN
通讯作者：
Akkerman, JWN
DOI：
10.1111/j.1538-7836.2011.04208.x
发表时间：
2011-04
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Rondina MT;Schwertz H;Harris ES;Kraemer BF;Campbell RA;Mackman N;Grissom CK;Weyrich AS;Zimmerman GA
通讯作者：
Zimmerman GA