Insulin resistance and vascular function.
It has become clear that amongst its many actions insulin is also a vasoactive hormone. Its effect to cause endothelial-nitric oxide-dependent vasodilation is physiologic and dose-dependent. Recent data suggest that insulin's metabolic and vascular actions are closely linked. Indeed, insulin resistant states, which by definition, exhibit diminished insulin-mediated glucose uptake into peripheral tissues also display impaired insulin mediated vasodilation as well as impaired endothelium dependent vasolidation to the muscarinic receptor agonist acetylcholine. Free fatty acids are elevated in states of insulin resistance and also cause endothelial dysfunction along with impaired insulin-mediated vasodilation. Thus, a picture is emerging linking insulin action in peripheral tissues to its action in endothelium. More recent data suggest that insulin signaling mechanisms in peripheral tissues and endothelium may be shared. Thus mechanisms causing insulin resistance via defects in insulin signaling might be expected to be manifest in both tissues. The protective action of nitric oxide and healthy endothelial function are critical to prevent atherosclerotic vascular disease. If follows that endothelial dysfunction associated insulin resistance through common defects in insulin signaling presents a parsimonious mechanism to account for the increased risk of cardiovascular disease associated with insulin resistance.
Baron
Alain D
AD
Indiana University School of Medicine, Indianapolis, IN, USA. abaron@amylin.com
D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D007866:Leg / Q000098:blood supply; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000098:blood supply; D012039:Regional Blood Flow; D014664:Vasodilation / Q000502:physiology*
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D016210:Methacholine Chloride