Oxidative stress and vascular disease in diabetes: is the dichotomization of insulin signaling still valid?
The current wisdom indicates that insulin's positive effects, normoglycemia, vasodilation, and anti-inflammation, are mediated by the canonical phosphoinositide 3-kinase (PI3K)/Akt pathway whereas the negative effects are mediated by the mitogen-activated protein kinase (MAPK)/extracellular regulated kinase (ERK) pathway. Much of the intracellular oxidant stress is mediated by the MAPK/ERK pathway which is a downstream signal also for other proatherogenic hormones such as angiotensin II. However, recent evidence links MAPK activation to antioxidant activity and vascular protection. We argue against a dichotomization of insulin signaling also in light of the concept that ERK-MAPK represents a critical node in the intracellular insulin network responsible for several positive effects related not only to vascular function but also to life span.
Avogaro
Angelo
A
Department of Clinical and Experimental Medicine, University of Padova, Medical School, Padova, Italy. angelo.avogaro@unipd.it
de Kreutzenberg
Saula Vigili
SV
Fadini
Gian Paolo
GP
D000818:Animals; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D007328:Insulin; D048049:Extracellular Signal-Regulated MAP Kinases