Abstract
A growing body of evidence suggests that oxidative stress plays a key role in the pathogenesis of micro-and macrovascular diabetic complications. The increased oxidative stress in subjects with type 2 diabetes is a consequence of several abnormalities, including hyperglycemia, insulin resistance, hyperinsulinemia, and dyslipidemia, each of which contributes to mitochondrial superoxide overproduction in endothelial cells of large and small vessels as well as the myocardium. The unifying pathophysiological mechanism that underlies diabetic complications could be explained by increased production of reactive oxygen species (ROS) via: (1) the polyol pathway flux, (2) increased formation of advanced glycation end products (AGEs), (3) increased expression of the receptor for AGEs, (4) activation of protein kinase C isoforms, and (5) overactivity of the hexosamine pathway. Furthermore, the effects of oxidative stress in individuals with type 2 diabetes are compounded by the inactivation of two critical anti-atherosclerotic enzymes: endothelial nitric oxide synthase and prostacyclin synthase. Of interest, the results of clinical trials in patients with type 2 diabetes in whom intensive management of all the components of the metabolic syndrome (hyperglycemia, hypercholesterolemia, and essential hypertension) was attempted (with agents that exert a beneficial effect on serum glucose, serum lipid concentrations, and blood pressure, respectively) showed a decrease in adverse cardiovascular end points. The purpose of this review is (1) to examine the mechanisms that link oxidative stress to micro-and macrovascular complications in subjects with type 2 diabetes and (2) to consider the therapeutic opportunities that are presented by currently used therapeutic agents which possess antioxidant properties as well as new potential antioxidant substances.
| Original language | English |
|---|---|
| Pages (from-to) | 313-324 |
| Number of pages | 12 |
| Journal | Current Diabetes Reviews |
| Volume | 7 |
| Issue number | 5 |
| Publication status | Published - Sep 2011 |
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Keywords
- Macrovascular complications
- Metabolic
- Microvascular complications
- Oxidative stress
- Type 2 diabetes mellitus
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Endocrinology
Cite this
The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus micro-and macrovascular complications : Avenues for a mechanistic-based therapeutic approach. / Folli, Franco; Corradi, Domenico; Fanti, Paolo; Davalli, Alberto; Paez, Ana; Giaccari, Andrea; Perego, Carla; Muscogiuri, Giovanna.
In: Current Diabetes Reviews, Vol. 7, No. 5, 09.2011, p. 313-324.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus micro-and macrovascular complications
T2 - Avenues for a mechanistic-based therapeutic approach
AU - Folli, Franco
AU - Corradi, Domenico
AU - Fanti, Paolo
AU - Davalli, Alberto
AU - Paez, Ana
AU - Giaccari, Andrea
AU - Perego, Carla
AU - Muscogiuri, Giovanna
PY - 2011/9
Y1 - 2011/9
N2 - A growing body of evidence suggests that oxidative stress plays a key role in the pathogenesis of micro-and macrovascular diabetic complications. The increased oxidative stress in subjects with type 2 diabetes is a consequence of several abnormalities, including hyperglycemia, insulin resistance, hyperinsulinemia, and dyslipidemia, each of which contributes to mitochondrial superoxide overproduction in endothelial cells of large and small vessels as well as the myocardium. The unifying pathophysiological mechanism that underlies diabetic complications could be explained by increased production of reactive oxygen species (ROS) via: (1) the polyol pathway flux, (2) increased formation of advanced glycation end products (AGEs), (3) increased expression of the receptor for AGEs, (4) activation of protein kinase C isoforms, and (5) overactivity of the hexosamine pathway. Furthermore, the effects of oxidative stress in individuals with type 2 diabetes are compounded by the inactivation of two critical anti-atherosclerotic enzymes: endothelial nitric oxide synthase and prostacyclin synthase. Of interest, the results of clinical trials in patients with type 2 diabetes in whom intensive management of all the components of the metabolic syndrome (hyperglycemia, hypercholesterolemia, and essential hypertension) was attempted (with agents that exert a beneficial effect on serum glucose, serum lipid concentrations, and blood pressure, respectively) showed a decrease in adverse cardiovascular end points. The purpose of this review is (1) to examine the mechanisms that link oxidative stress to micro-and macrovascular complications in subjects with type 2 diabetes and (2) to consider the therapeutic opportunities that are presented by currently used therapeutic agents which possess antioxidant properties as well as new potential antioxidant substances.
AB - A growing body of evidence suggests that oxidative stress plays a key role in the pathogenesis of micro-and macrovascular diabetic complications. The increased oxidative stress in subjects with type 2 diabetes is a consequence of several abnormalities, including hyperglycemia, insulin resistance, hyperinsulinemia, and dyslipidemia, each of which contributes to mitochondrial superoxide overproduction in endothelial cells of large and small vessels as well as the myocardium. The unifying pathophysiological mechanism that underlies diabetic complications could be explained by increased production of reactive oxygen species (ROS) via: (1) the polyol pathway flux, (2) increased formation of advanced glycation end products (AGEs), (3) increased expression of the receptor for AGEs, (4) activation of protein kinase C isoforms, and (5) overactivity of the hexosamine pathway. Furthermore, the effects of oxidative stress in individuals with type 2 diabetes are compounded by the inactivation of two critical anti-atherosclerotic enzymes: endothelial nitric oxide synthase and prostacyclin synthase. Of interest, the results of clinical trials in patients with type 2 diabetes in whom intensive management of all the components of the metabolic syndrome (hyperglycemia, hypercholesterolemia, and essential hypertension) was attempted (with agents that exert a beneficial effect on serum glucose, serum lipid concentrations, and blood pressure, respectively) showed a decrease in adverse cardiovascular end points. The purpose of this review is (1) to examine the mechanisms that link oxidative stress to micro-and macrovascular complications in subjects with type 2 diabetes and (2) to consider the therapeutic opportunities that are presented by currently used therapeutic agents which possess antioxidant properties as well as new potential antioxidant substances.
KW - Macrovascular complications
KW - Metabolic
KW - Microvascular complications
KW - Oxidative stress
KW - Type 2 diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=80053515769&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80053515769&partnerID=8YFLogxK
M3 - Article
C2 - 21838680
AN - SCOPUS:80053515769
VL - 7
SP - 313
EP - 324
JO - Current Diabetes Reviews
JF - Current Diabetes Reviews
SN - 1573-3998
IS - 5
ER -