Insulin resistance accounts for glucotoxicity observed in diabetes and atherosclerotic disease. Glucotoxicity depends from the shift of glucose metabolism from the glycolytic pathway to minor forms of glucose metabolism, including sorbitol, hexosamine and AGE pathways. These pathways increase oxidative stress and/or block insulin signalling so leading to a further decline of insulin action. A genetic defect of insulin action (the g972R Insulin Receptor Substrate 1 variant) may sustain endothelial dysfunction, the first defect of vascular homeostasis in the road to atherosclerosis. Furthermore, hyperglycemia even in the absence of insulin resistance, activates the hexosamine pathway in endothelial cells, affects the production of nitric oxide, increases the production and activity of metalloproteinase 2 and 9 and activates endothelium thus provoking endothelial dysfunction. Oxidative stress and inflammation through activation of IKK-beta could determine insulin resistance impairing IRS-1 ability to activate the metabolic branch of insulin signalling. Furthermore, increased oxidative stress may be speculated to affect glucose metabolism in a proportion of patients with coronary artery disease. In conclusion, type 2 diabetes and atherosclerosis share vascular homeostasis and glucose metabolism and insulin resistance might be the common road where diabetes and atherosclerosis run together. © 2005 Blackwell Publishing Ltd.

Federici, M., & Lauro, R. (2005). Review article: diabetes and atherosclerosis--running on a common road. ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 22(Suppl 2), 11-15 [10.1111/j.1365-2036.2005.02617.x].

Review article: diabetes and atherosclerosis--running on a common road

FEDERICI, MASSIMO;LAURO, RENATO
2005

Abstract

Insulin resistance accounts for glucotoxicity observed in diabetes and atherosclerotic disease. Glucotoxicity depends from the shift of glucose metabolism from the glycolytic pathway to minor forms of glucose metabolism, including sorbitol, hexosamine and AGE pathways. These pathways increase oxidative stress and/or block insulin signalling so leading to a further decline of insulin action. A genetic defect of insulin action (the g972R Insulin Receptor Substrate 1 variant) may sustain endothelial dysfunction, the first defect of vascular homeostasis in the road to atherosclerosis. Furthermore, hyperglycemia even in the absence of insulin resistance, activates the hexosamine pathway in endothelial cells, affects the production of nitric oxide, increases the production and activity of metalloproteinase 2 and 9 and activates endothelium thus provoking endothelial dysfunction. Oxidative stress and inflammation through activation of IKK-beta could determine insulin resistance impairing IRS-1 ability to activate the metabolic branch of insulin signalling. Furthermore, increased oxidative stress may be speculated to affect glucose metabolism in a proportion of patients with coronary artery disease. In conclusion, type 2 diabetes and atherosclerosis share vascular homeostasis and glucose metabolism and insulin resistance might be the common road where diabetes and atherosclerosis run together. © 2005 Blackwell Publishing Ltd.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/09 - Medicina Interna
Settore M-EDF/01 - Metodi e Didattiche delle Attivita' Motorie
English
Con Impact Factor ISI
hexosamine; metalloproteinase; metalloproteinase 2; metalloproteinase 9; sorbitol; unclassified drug; atherosclerosis; coronary artery disease; diabetes mellitus; genetic disorder; genetics; glucose metabolism; glycolysis; human; hypercholesterolemia; hyperglycemia; insulin resistance; maturity onset diabetes mellitus; metabolic syndrome X; oxidative stress; pathophysiology; priority journal; review; smoking; Atherosclerosis; Diabetes Mellitus, Type 2; Endothelium, Vascular; Glucose; Homeostasis; Humans; Hyperglycemia; Insulin; Insulin Resistance; Models, Biological; Oxidative Stress
Federici, M., & Lauro, R. (2005). Review article: diabetes and atherosclerosis--running on a common road. ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 22(Suppl 2), 11-15 [10.1111/j.1365-2036.2005.02617.x].
Federici, M; Lauro, R
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/39947
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