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2000 Fiscal Year Final Research Report Summary

Association between platelet aggregation and diabetic complication in diabetes mellitus

Research Project

Project/Area Number 09671040
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionGIFU UNIVERSITY

Principal Investigator

ISHIZUKA Tatsuo  Department of General Medicine, GIFU UNIVERSITY, Professor, 医学部・附属病院, 教授 (20108070)

Project Period (FY) 1997 – 2000
KeywordsDiabetic complication / platelet aggregation / PKC / serotonin release / hypertension / leptin
Research Abstract

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

  • Research Products

    (23 results)

All Other

All Publications (23 results)

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

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      「研究成果報告書概要(和文)」より
  • [Publications] T.Ishizuka et al.: "Differential effect of antidiabetic thiazolidinediones, troglitazone and pioglitazone on human platelet aggregation mechanism."Diabetes. 47. 1494-1500 (1998)

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  • [Publications] T.Ishizuka et al.: "Dehydroepiandrosterone improves glucose uptake via activations of protein kinase C and phosphatidylinositol 3-kinase"American J Pysiology : Endocrinology and Metabolism. 276,. E196-E204 (1999)

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      「研究成果報告書概要(和文)」より
  • [Publications] K.Kajita, T.Ishizuka et al.: "The role of atypical and conventional PKC in dehydroepiandrosterone-induced glucose uptake and dexamethasone-induced insulin resistance."Biochem Biophys Res Commun. 277. 361-367 (2000)

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  • [Publications] M.Kimura, T.Ishizuka, et al.: "Platelet protein kinase C(PKC)isoform content in type 2 diabetes complicated with retinopathy and nephropathy"Platelets. (in press). (2001)

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      「研究成果報告書概要(和文)」より
  • [Publications] K.Kajita, T.Ishizuka et al.: "Glucocorticoid-induced insulin resistance associates with activation of protein kinase C isoforms"Cellular Signalling. (in press). (2001)

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  • [Publications] 三浦淳、石塚達夫 他: "OLETF研究会記録 第4巻 OLETFラットでのDHEA経口摂取による耐糖能改善効果"OLETF研究会編集. 153 (1998)

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  • [Publications] 石塚達夫、安田圭吾: "副腎皮質ステロイド剤"内科学"第7版"朝倉書店、東京. 1462-1464 (1999)

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  • [Publications] T.Ishizuka, J.Hoffman, D.R.Cooper, J.E.Watson, D.B.Pushkin, R.V.Farese: "Glucose-induced synthesis of diacylglycerol de novo is associated with translocation(activation)of protein kinase C in rat adipocytes"FEBS Lett.. Vol.249. 234-238 (1989)

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  • [Publications] T.Ishizuka, D.R.Cooper, R.V.Farese: "Insulin stimulates the traslocation of protein kinase C in rat adipocytes"FEBS Lett.. Vol.257. 337-340 (1989)

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  • [Publications] T.Ishizuka, D.R.Cooper, H.Hernandez, D.Buckley, M.L.Standaert, R.V.Farese: "Effects of insulin on diacylglycerol-protein kinase C signaling in rat diaphragm and soleus muscles and relationship to glucose trasport."Diabetes. Vol.39. 181-190 (1990)

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  • [Publications] T.Ishizuka, D.R.Cooper, R.V.Farese: "Insulin provokes apparent increases in rat adipocytes M-kinase."Biochem. Biopophys. Res.Commun. Vol.169. 966-972 (1990)

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  • [Publications] T.Ishizuka, K.Yasuda, N.Takeda, K.Kajita, K.Miura, S.Nakashima, S.Nagao, Y.Nozawa: "Thrombin-induced breakdown of phosphoinositides in platelets from patients with NIDDM"Endocrinologia Japonica. Vol.38. 81-87 (1991)

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  • [Publications] T.Ishizuka, D.R.Cooper, T.Arnold, H.Hernandez, R.V.Farese: "Downregulation of PKC and insulin-stimulated 2-deoxyglucose uptake in rat adipocytes by phorbol Esters"Glucose an Insulin. Diabetes. Vol.40. 1274-1281 (1991)

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  • [Publications] 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)

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  • [Publications] J.L.Messina, M.L.Standaert, T.Ishizuka, R.S.Weinstock, R.V.Farese: "Role of protein kinase C in instulin's regulation of c-fos transcription"J.Biol.chem.. Vol.267. 9223-9228 (1992)

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  • [Publications] T.Ishizuka, M.Yamamoto, K.Kajita, K.Yasuda, K.Miura, H.Hernandez, R.V.Farese: "Differential effect of aging on protein kinase C in rat adipocytes and soleus muascle."Metabolism. Vol.42. 420-425 (1993)

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  • [Publications] 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."Diabetorogia. Vol.37. 632-638 (1994)

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  • [Publications] T.Ishizuka, M.Yamamoto, K.Kajita, T.Nagashima, O.Taniguchi, H.Wada, S.ItayaK, K.Yasuda: "Phorbol ester and insulim stimulate protein kinase C isoforms in rat adipocytes."Diabetes Research and Clinical Practice. Vol.26. 91-99 (1994)

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  • [Publications] T.Ishizuka, M.Yamamoto, T.Nagashima, K.Kajita, O.Tanoguchi, K.Yasuda, K.Miura: "Effect of dexamethasone and prednisolone on insulin-induced activation of protein kinase C in rat adipocytes and soleus muscles"Metabolism. Vol.44. 298-306 (1995)

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  • [Publications] T.Ishizuka, H.Morita, T.Mune, H.Daidoh, J.Hanafusa, M.Yamamoto, T.Shibata, K.Yasuda: "Growth hormone secretion in human acromegalic pituitary adenomas : cyclic adenosine monophosphate and and protein kinase C responses"Metabolism. Vol.45. 206-210 (1995)

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  • [Publications] T.Ishizuka, T.Nagashima, M.Yamamoto, K, Kajita, K.Yamada, H.Wada, S.Itaya, K.Yasuda, Y.Nozawa: "Effects of wortmannin on glucose uptake and protein kinase C activity in rat adipocytes."Diabetes Research and Clinical Practice. Vol.29. 143-152 (1995)

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  • [Publications] T.Ishizuka, K.Kajita, K.Yamada, A.Miura, Y.Kanoh, M.Ishizuka, H.Wada, S.Itaya, M.Yamamoto, K.Yasuda, K.Nagata, Y.Okano: "Insulin regulates PKC isoform m-RNA in rat adipocytes"Diabetes Res.Clin.Pract.. Vol.33. 159-167 (1996)

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Published: 2002-03-26  

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