title: Linking the beneficial effects of current therapeutic approaches in diabetes to the vascular endothelin system.
abstract: The rising epidemic of diabetes worldwide is of significant concern. Although the ultimate objective is to prevent the development and find a cure for the disease, prevention and treatment of diabetic complications is very important. Vascular complications in diabetes, or diabetic vasculopathy, include macro- and microvascular dysfunction and represent the principal cause of morbidity and mortality in diabetic patients. Endothelial dysfunction plays a pivotal role in the development and progression of diabetic vasculopathy. Endothelin-1 (ET-1), an endothelial cell-derived peptide, is a potent vasoconstrictor with mitogenic, pro-oxidative and pro-inflammatory properties that are particularly relevant to the pathophysiology of diabetic vasculopathy. Overproduction of ET-1 is reported in patients and animal models of diabetes and the functional effects of ET-1 and its receptors are also greatly altered in diabetic conditions. The current therapeutic approaches in diabetes include glucose lowering, sensitization to insulin, reduction of fatty acids and vasculoprotective therapies. However, whether and how these therapeutic approaches affect the ET-1 system remain poorly understood. Accordingly, in the present review, we will focus on experimental and clinical evidence that indicates a role for ET-1 in diabetic vasculopathy and on the effects of current therapeutic approaches in diabetes on the vascular ET-1 system.
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan. Electronic address: t-matsu@hoshi.ac.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Pharmacology, Medical School of Ribeirao Preto, University of Sao Paulo, Av Bandeirantes 3900, Ribeirao Preto, SP 14049-900, Brazil.
authors.forename: Rheure A M
authors.initials: RA
authors.lastname: Lopes
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Pharmacology, Medical School of Ribeirao Preto, University of Sao Paulo, Av Bandeirantes 3900, Ribeirao Preto, SP 14049-900, Brazil.
authors.forename: Rita C
authors.initials: RC
authors.lastname: Tostes
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017466:Receptors, Endothelin / Q000378:metabolism
chemical_list: D016232:Endothelins; D017466:Receptors, Endothelin
keywords: Diabetes; ET-1; Endothelial dysfunction; Type 2 diabetes; Vascular smooth muscle