Summary
This study was aimed to evaluate the significance and mechanism of vascular endothelial dysfunction in diabetic patients. Thirty-eight patients with type 2 diabetes mellitus were categorized to 3 groups according to the grade of retinopathy and treated for 4 weeks randomly with glibenclamide (n = 14) or troglitazone (n = 24). While plasma tissue plasminogen activator (tPA) (23.9 vs. 8.9 ng/ml; P< 0.05) and plasminogen activator inhibitor-1 (PAI-1) (23.6 vs. 11.8 pg/ml; P< 0.05) levels were significantly elevated in type 2 diabetes patients compared to the control subjects, the PAI-1 titer, but not tPA, was correlated with the severity of retinopathy. Four weeks-treatment by troglitazone was associated with significant reduction of PAI-1 level (20.1 from 26.8 pg/ml, P< 0.05), but not that of tPA, which was correlated with reduction of the steady state plasma glucose (SSPG) titer, but not with that of fasting plasma glucose. Immunoreactive PAI-1 or endothelin-1 (ET-1) were measured by ELISA in culture medium of human umbilical vein endothelial cells (HuVEC) or bovine vascular endothelial cells (bVEC), respectively, in the presence or absence of test agents (insulin, thiazolidinediones, 15-deoxy-delta 12, 14-prostaglandin J2 (15d-PGJ2), bezafibrate). Thiazolidinediones inhibited tumor necrosis factor α (TNF- α )-stimulated PAI-1 secretion and mRNA expression in a dosedependent fashion. Thiazolidinediones and 15d-PGJ2, but not bezafibrate, inhibited basal and insulin-stimulated ET-1 secretion and mRNA expression in a dose-dependent fashion.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Chien KL, Lee YT, Sung FC, Hsu HC, Su TC, Lin RS (1999) Hyperinsulinemia and related atherosclerotic nsk factors in the population at cardiovascular risk: a community-based study Clinical Chemistry 45: 838–46
Haffner SM, D’Agno R Jr, Mykkanen L, Tracy R, Howard B, Rewers M, Selby J, Savage PJ, Saad MF (1999) Insulin sensitivity in subjects with type 2 diabetes. Relationship to cardiovascular risk factors. Diabetes Care 22: 562–8
Festa A, D’Agostino LB, Mykkanen L, Tracy RP, Zaccaro DJ, Hales CN, Haffner SM (1999) Relative contribution of insulin and its precursors to fibrinogen and PAI-1 in a large population with different states of glucose tolerance. Arteriosclerosis, Thrombosis & Vascular Biology 19: 562–8
Wagenknecht LE, D’Agostino LB, Haffner SM, Savage PJ, Rewers M (1998) Impaired glucose tolerance, type 2 diabetes, and carotid wall thickness: the Insulin Resistance Atherosclerosis Study. Diabetes Care 21: 1812–8
Eckel RH (1998) Insulin resistance in atherosclerosis. American Journal of Clinical Nutrition 65: 164–5
Nolan JJ, D’Agostino LB, Haffner SM, Savage PJ, (1994) Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. New England Journal of Medicine 331: 1183–93
Jürgen M, Linda BM, Tracey ASO, William OW, Timothy MW, Steven AK (1995) An antidiabetic Thiazolidinedion is a high affinity ligand for Peroxisome Proliferator-activated Receptor γ(PPARγ). The Journal of Biological Chemistry 270: 129–653
Lindgren A, Lindoff C, Norrving B, Johansson RB (1996) Tissue plasminogen activator and plasminogen activator inhibitor-1 in stroke patients. Stroke 27: 1066–71
Matsuda T, Morishita E, Jokaji H, Saito M, Kumabashiri L, Akakura H, Uotani C, Yamazaki M (1995) Plasminogen activator inhibitor in plasma and arteriosclerosis. Annals of the New York Academy of Sciences 748: 394–8
Gray RP, Patterson DL, Yudkin JS (1993) Plasminogen activator inhibitor activity in diabetic and nondiabetic survivors of myocardial infarction. Arteriosclerosis & Thrombosis 13: 415–20
Keber I, Keber D. (1992) Increased plasminogen activator inhibitor activity in survivors of myocardial infarction is associated with metabolic risks factors of atherosclerosis. Haemostasis 22: 187–94
Fern C, Bellini C, Desideri G, De Mattia G, Santucci A (1996) Endogenous insulin modulates circulating endothelin-1 concentrations in humans. Diabetes Care 19: 504–6
Nakayama T, Numata Y, Kawada M, Kurokawa H. Nakamura T, Hashimoto K (1993) Hypermeability of abdominal capillary vessels to endothelin-1 in patients with diabetes mellitus. Journal of Cardiovascular Pharmacology 22:S360–423
Pieper GM (1998) Review of alterations in endothelial nitric oxide production in diabetes: protective role of arginine on endothelial dysfunction. Hypertension 31: 1047–60
Stevens RB. Sutherland DE, Ansite JD, Saxena M. Rossini TJ, Levay-Young BK, Hering BJ, Mills CD (1997) Insulin down-regulates the inducible nitric oxide synthase pathway: nitric oxide as cause and effect of diabetes?. Journal of Immunology 159: 5329–35
Sobrevia L. Maan GE (1997) Dysfunction of the endothelial nitric oxide signaling pathway in diabetes and hyperglycaemia. Experimental Physiology 82: 423–52
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer-Verlag Tokyo
About this paper
Cite this paper
Yamada, D. et al. (2000). Improvement by Thiazolidinediones of Vascular Endothelial Cell Dysfunction in Diabetic Patients: A Possible New Physiological Role of PPARγ. In: Kita, T., Yokode, M. (eds) Lipoprotein Metabolism and Atherogenesis. Springer, Tokyo. https://doi.org/10.1007/978-4-431-68424-4_16
Download citation
DOI: https://doi.org/10.1007/978-4-431-68424-4_16
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-68426-8
Online ISBN: 978-4-431-68424-4
eBook Packages: Springer Book Archive