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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:889.)
© 2005 American Heart Association, Inc.

Editorials

The Union of Vascular and Metabolic Actions of Insulin in Sickness and in Health

Jeong-a Kim; Kwang Kon Koh; Michael J. Quon

From the Diabetes Unit, NCCAM (J.K., M.J.Q.), National Institutes of Health, Bethesda, Md; and the Vascular Medicine and Atherosclerosis Unit (K.K.K.), Cardiology, Gil Heart Center, Gachon Medical School, Incheon, Korea.

Correspondence to Michael J. Quon, MD, PhD, Chief, Diabetes Unit, NCCAM, NIH, 10 Center Drive, Building 10, Room 6C-205, Bethesda, MD 20892-1632. E-mail quonm@nih.gov

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Disorders of metabolic homeostasis including type 2 diabetes, obesity, and dyslipidemias are characterized by both insulin resistance and endothelial dysfunction.¹ Insulin resistance and endothelial dysfunction are also prominent features of important cardiovascular disorders including hypertension, coronary artery disease, and atherosclerosis.² Indeed, insulin resistance is thought to be the tie that binds metabolic and cardiovascular disorders together in an unhappy union called the metabolic syndrome (aka the insulin resistance syndrome).^3,4 Although these associations are well established, molecular mechanisms explaining the underlying pathophysiology are not completely understood. Interestingly, inflammation mediated by innate immune signaling pathways has been implicated in both metabolic insulin resistance and vascular endothelial dysfunction.^1,5,6 In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Kim et al demonstrate that treatment of vascular endothelial cells with the free fatty acid (FFA) palmitate activates IKKß (a proinflammatory signaling molecule), impairs insulin signaling, and decreases insulin-stimulated production of nitric oxide (NO).⁷ Importantly, inhibitory effects of FFA treatment on insulin signaling and NO production are blocked by overexpression of a dominant inhibitory mutant of IKKß. Moreover, deleterious effects of FFA treatment are recapitulated by overexpression of wild-type IKKß. Thus, Kim et al have uncovered an additional link between metabolic and vascular pathophysiology that helps to explain mechanisms underlying the metabolic syndrome and related cardiovascular diseases. To understand the importance of these findings it is useful to review the mechanisms coupling vascular and metabolic physiology, the role of inflammation in insulin resistance, and the role of insulin resistance to couple vascular and metabolic pathophysiology . . . [Full Text of this Article]

Related Article:

Free Fatty Acid Impairment of Nitric Oxide Production in Endothelial Cells Is Mediated by IKKß

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Arterioscler Thromb Vasc Biol 2005 25: 989-994. [Abstract] [Full Text] [PDF]

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