Association between platelet aggregation and diabetic complication in diabetes mellitus

糖尿病患者血小板聚集与糖尿病并发症的关系

• 批准号: 09671040
• 负责人: ISHIZUKA Tatsuo
• 金额: $ 1.92万
• 依托单位: GIFU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671040/
• 关键词: Diabetic complication; platelet aggregation; PKC; serotonin release; hypertension; leptin; 糖尿病; トロンビン; イノシトール隣脂質 代謝; セロトニン; 高血圧; PKC阻害剤; rhoA; 低分子量G蛋白; 糖尿病性網膜症; 糖尿病性腎症; phosphatidy linositol 3-kinase

1)Plalelet PKC β immunoreacitivity in cytosol fraction was siguificantly higher in diabetic patients with normal serum creatinine(Cr)level than in diabetic patients with abnormal Cr level(Cr ≧ 15 mg/dl)or in healthy subjects. Platelet PKCβ immunoreactivity in cytosol from diabetic patients treated with sulphonylurea was significantly higher than that from healthy subujects. In addition, PKCβ immunoreactivity in diabetic patients with insulin treatment was significantly suppressed compared to that in patients treated by sulphonylurea treatment. These results suggest that chronic hyperglyecmia may activate platelet PKCβ isoform, and that insulin treatment may decrease platelet PKCβ activity.2)It has been reported that the presence of hypertension in diabetes causes a decrease in intraplatelet serotonin content. We investigated 0.1 U/ml thrombin-sutimulated[^<14>C]serotonin release from platelet in 17 diabetic subjects. Thrombin-induced serotonin release from platelet in diabetic subjects … More was significantly increased, compared with controls and hypertension without diabetes. Thrombin-induced platelet serotonin release in diabetic patients with hypertension was significantly higher than in diabetic patients without hypertension. There was no significant correlation among the severities of diabetic complication, and diabetic treatment in thrombin-induced serotonin release from 17 diabetic patients. Increased serotonin release from platelet in diabetes may contribute to the development of macroangiopathy in diabetes with hypertension.3)We studied serum leptin concentration ard agonist-induced platelet aggregation in platelets from 13 diabetic subujects who did not use the medicine which influenced the platelet function, and 9 contorol subjects(6 men, 3 woman, average age 32.4 ±13.6 years old, and average BMI 23.0±2.5 kg/m^2). It was observed positive correlation between the serum leptin concentration and BMI in both diabetic and control subjects. There was no significant difference of serum leptin concentration in diabetic subjects with and withouto diabetic complication. These results suggest that ADP-stimulated maximum platelet aggregation rate may be associated with serum leptin concentration in diabetic subjects. Less

1)血清肌酐(Cr)水平正常的糖尿病患者胞浆部分中的血小板PKCβ免疫反应性显着高于Cr水平异常(Cr≥15 mg/dl)的糖尿病患者或健康受试者。接受磺脲类药物治疗的糖尿病患者胞浆中血小板 PKCβ 免疫反应性显着高于健康受试者。此外，与接受磺脲类治疗的患者相比，接受胰岛素治疗的糖尿病患者的 PKCβ 免疫反应性显着受到抑制。这些结果表明，慢性高血糖可能激活血小板PKCβ亚型，胰岛素治疗可能降低血小板PKCβ活性。2)据报道，糖尿病患者存在高血压，导致血小板内血清素含量减少。我们研究了17名糖尿病受试者中血小板中0.1U/ml凝血酶刺激的[^ 14 C]血清素释放。与对照组和非糖尿病高血压患者相比，糖尿病受试者中凝血酶诱导的血小板血清素释放显着增加。合并高血压的糖尿病患者凝血酶诱导的血小板血清素释放显着高于无高血压的糖尿病患者。 17 名糖尿病患者的凝血酶诱导的血清素释放量与糖尿病并发症的严重程度和糖尿病治疗之间没有显着相关性。糖尿病患者血小板释放的血清素增加可能导致糖尿病合并高血压患者发生大血管病。3)我们研究了 13 名未使用影响血小板功能的药物的糖尿病受试者和 9 名对照受试者（6 名男性，3 名女性，平均年龄 32.4 ±13.6 岁，和 平均体重指数 23.0±2.5 kg/m^2)。在糖尿病和对照受试者中观察到血清瘦素浓度与体重指数呈正相关。有或没有糖尿病并发症的糖尿病受试者的血清瘦素浓度没有显着差异。这些结果表明，ADP 刺激的最大血小板聚集率可能与糖尿病受试者的血清瘦素浓度相关。较少的

项目成果

K.Kajita, T.Ishizuka et al.: "Glucocorticoid-induced insulin resistance associates with activation of protein kinase C isoforms"Cellular Signalling. (in press). (2001)

K.Kajita、T.Ishizuka 等人：“糖皮质激素诱导的胰岛素抵抗与蛋白激酶 C 亚型的激活相关”细胞信号传导。

T.Ishizuka, M.Yamamoto, K.Kajita, T.Nagashima, K.Yasuda, K.Miura, D.R.Cooper, R.V.Farese: "Insulin stimulates novel protein kinase C in rat adipocytes."Biochem. Biophys. Res.Commun. Vol.183. 814-820 (1992)

T.Ishizuka、M.Yamamoto、K.Kajita、T.Nagashima、K.Yasuda、K.Miura、D.R.Cooper、R.V.Farese：“胰岛素刺激大鼠脂肪细胞中的新型蛋白激酶 C。”Biochem。

T.Ishizuka, O.Taniguchi, M.Yamamoto, K.Kajita, T.Nagashima, N.Takeda, H.Inoue, K.Yasuda, K.Miura: "Thrombin-induced platelet aggregation, phosphoinositide matabolisum and protein phosphorylation in NIDDM patients treated by diet, sulphonylurea or insulin.

T.Ishizuka、O.Taniguchi、M.Yamamoto、K.Kajita、T.Nagashima、N.Takeda、H.Inoue、K.Yasuda、K.Miura：“NIDDM 中凝血酶诱导的血小板聚集、磷酸肌醇代谢和蛋白质磷酸化

H.Wada,T.Ishizuka: "Inhibitory effect of glyburide on thrombin-induced platelet aggregation and phosphoinositide metabolism in normal human platelets."Platelets. 10. 45-51 (1999)

H.Wada，T.Ishizuka：“格列本脲对正常人血小板中凝血酶诱导的血小板聚集和磷酸肌醇代谢的抑制作用。”血小板。

T.Ishizuka et al: "Alterations in insulin-induced postreceptor signaling in adipocytes of Otsuka Long-Evans Tokushima fatty(OLETE)strain" J.Endocrinology. 156. 1-13 (1998)

T.Ishizuka 等人：“Otsuka Long-Evans Tokushima 脂肪 (OLETE) 菌株脂肪细胞中胰岛素诱导的后受体信号传导的改变”J.Endocrinology。