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Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo
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| Zeitschriftentitel: | Diabetes |
|---|---|
| Personen und Körperschaften: | , , , , , , , , |
| In: | Diabetes, 53, 2004, 5, S. 1344-1351 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Diabetes Association
|
| Schlagwörter: |
| author_facet |
Ceolotto, Giulio Bevilacqua, Michela Papparella, Italia Baritono, Elisabetta Franco, Lorenzo Corvaja, Carlo Mazzoni, Martina Semplicini, Andrea Avogaro, Angelo Ceolotto, Giulio Bevilacqua, Michela Papparella, Italia Baritono, Elisabetta Franco, Lorenzo Corvaja, Carlo Mazzoni, Martina Semplicini, Andrea Avogaro, Angelo |
|---|---|
| author |
Ceolotto, Giulio Bevilacqua, Michela Papparella, Italia Baritono, Elisabetta Franco, Lorenzo Corvaja, Carlo Mazzoni, Martina Semplicini, Andrea Avogaro, Angelo |
| spellingShingle |
Ceolotto, Giulio Bevilacqua, Michela Papparella, Italia Baritono, Elisabetta Franco, Lorenzo Corvaja, Carlo Mazzoni, Martina Semplicini, Andrea Avogaro, Angelo Diabetes Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo Endocrinology, Diabetes and Metabolism Internal Medicine |
| author_sort |
ceolotto, giulio |
| spelling |
Ceolotto, Giulio Bevilacqua, Michela Papparella, Italia Baritono, Elisabetta Franco, Lorenzo Corvaja, Carlo Mazzoni, Martina Semplicini, Andrea Avogaro, Angelo 0012-1797 1939-327X American Diabetes Association Endocrinology, Diabetes and Metabolism Internal Medicine http://dx.doi.org/10.2337/diabetes.53.5.1344 <jats:p>Oxidative stress may be involved in the development of vascular complications associated with diabetes; however, the molecular mechanism responsible for increased production of free radicals in diabetes remains uncertain. Therefore, we examined whether acute hyperinsulinemia increases the production of free radicals and whether this condition affects proliferative extracellular signal-regulated kinase (ERK-1 and -2) signaling in human fibroblasts in vitro. Insulin treatment significantly increased intracellular superoxide anion (O2−) production, an effect completely abolished by Tiron, a cell-permeable superoxide dismutase (SOD) mimetic and by polyethylene glycol (PEG)-SOD, but not by PEG catalase. Furthermore, insulin-induced O2− production was attenuated by the NAD(P)H inhibitor apocynin, but not by rotenone or oxypurinol. Inhibition of the phosphatidylinositol 3′-kinase (PI 3′-kinase) pathway with LY294002 blocked insulin-stimulated O2− production, suggesting a direct involvement of PI 3′-kinase in the activation of NAD(P)H oxidase. The insulin-induced free radical production led to membranous translocation of p47phox and markedly enhanced ERK-1 and -2 activation in human fibroblasts. In conclusion, these findings provided direct evidence that elevated insulin levels generate O2− by an NAD(P)H-dependent mechanism that involves the activation of PI 3′-kinase and stimulates ERK-1- and ERK-2-dependent pathways. This effect of insulin may contribute to the pathogenesis and progression of cardiovascular disease in the insulin resistance syndrome.</jats:p> Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo Diabetes |
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American Diabetes Association, 2004 |
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American Diabetes Association, 2004 |
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| title |
Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo |
| title_unstemmed |
Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo |
| title_full |
Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo |
| title_fullStr |
Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo |
| title_full_unstemmed |
Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo |
| title_short |
Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo |
| title_sort |
insulin generates free radicals by an nad(p)h, phosphatidylinositol 3′-kinase-dependent mechanism in human skin fibroblasts ex vivo |
| topic |
Endocrinology, Diabetes and Metabolism Internal Medicine |
| url |
http://dx.doi.org/10.2337/diabetes.53.5.1344 |
| publishDate |
2004 |
| physical |
1344-1351 |
| description |
<jats:p>Oxidative stress may be involved in the development of vascular complications associated with diabetes; however, the molecular mechanism responsible for increased production of free radicals in diabetes remains uncertain. Therefore, we examined whether acute hyperinsulinemia increases the production of free radicals and whether this condition affects proliferative extracellular signal-regulated kinase (ERK-1 and -2) signaling in human fibroblasts in vitro. Insulin treatment significantly increased intracellular superoxide anion (O2−) production, an effect completely abolished by Tiron, a cell-permeable superoxide dismutase (SOD) mimetic and by polyethylene glycol (PEG)-SOD, but not by PEG catalase. Furthermore, insulin-induced O2− production was attenuated by the NAD(P)H inhibitor apocynin, but not by rotenone or oxypurinol. Inhibition of the phosphatidylinositol 3′-kinase (PI 3′-kinase) pathway with LY294002 blocked insulin-stimulated O2− production, suggesting a direct involvement of PI 3′-kinase in the activation of NAD(P)H oxidase. The insulin-induced free radical production led to membranous translocation of p47phox and markedly enhanced ERK-1 and -2 activation in human fibroblasts. In conclusion, these findings provided direct evidence that elevated insulin levels generate O2− by an NAD(P)H-dependent mechanism that involves the activation of PI 3′-kinase and stimulates ERK-1- and ERK-2-dependent pathways. This effect of insulin may contribute to the pathogenesis and progression of cardiovascular disease in the insulin resistance syndrome.</jats:p> |
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| author | Ceolotto, Giulio, Bevilacqua, Michela, Papparella, Italia, Baritono, Elisabetta, Franco, Lorenzo, Corvaja, Carlo, Mazzoni, Martina, Semplicini, Andrea, Avogaro, Angelo |
| author_facet | Ceolotto, Giulio, Bevilacqua, Michela, Papparella, Italia, Baritono, Elisabetta, Franco, Lorenzo, Corvaja, Carlo, Mazzoni, Martina, Semplicini, Andrea, Avogaro, Angelo, Ceolotto, Giulio, Bevilacqua, Michela, Papparella, Italia, Baritono, Elisabetta, Franco, Lorenzo, Corvaja, Carlo, Mazzoni, Martina, Semplicini, Andrea, Avogaro, Angelo |
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| description | <jats:p>Oxidative stress may be involved in the development of vascular complications associated with diabetes; however, the molecular mechanism responsible for increased production of free radicals in diabetes remains uncertain. Therefore, we examined whether acute hyperinsulinemia increases the production of free radicals and whether this condition affects proliferative extracellular signal-regulated kinase (ERK-1 and -2) signaling in human fibroblasts in vitro. Insulin treatment significantly increased intracellular superoxide anion (O2−) production, an effect completely abolished by Tiron, a cell-permeable superoxide dismutase (SOD) mimetic and by polyethylene glycol (PEG)-SOD, but not by PEG catalase. Furthermore, insulin-induced O2− production was attenuated by the NAD(P)H inhibitor apocynin, but not by rotenone or oxypurinol. Inhibition of the phosphatidylinositol 3′-kinase (PI 3′-kinase) pathway with LY294002 blocked insulin-stimulated O2− production, suggesting a direct involvement of PI 3′-kinase in the activation of NAD(P)H oxidase. The insulin-induced free radical production led to membranous translocation of p47phox and markedly enhanced ERK-1 and -2 activation in human fibroblasts. In conclusion, these findings provided direct evidence that elevated insulin levels generate O2− by an NAD(P)H-dependent mechanism that involves the activation of PI 3′-kinase and stimulates ERK-1- and ERK-2-dependent pathways. This effect of insulin may contribute to the pathogenesis and progression of cardiovascular disease in the insulin resistance syndrome.</jats:p> |
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| imprint | American Diabetes Association, 2004 |
| imprint_str_mv | American Diabetes Association, 2004 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
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| spelling | Ceolotto, Giulio Bevilacqua, Michela Papparella, Italia Baritono, Elisabetta Franco, Lorenzo Corvaja, Carlo Mazzoni, Martina Semplicini, Andrea Avogaro, Angelo 0012-1797 1939-327X American Diabetes Association Endocrinology, Diabetes and Metabolism Internal Medicine http://dx.doi.org/10.2337/diabetes.53.5.1344 <jats:p>Oxidative stress may be involved in the development of vascular complications associated with diabetes; however, the molecular mechanism responsible for increased production of free radicals in diabetes remains uncertain. Therefore, we examined whether acute hyperinsulinemia increases the production of free radicals and whether this condition affects proliferative extracellular signal-regulated kinase (ERK-1 and -2) signaling in human fibroblasts in vitro. Insulin treatment significantly increased intracellular superoxide anion (O2−) production, an effect completely abolished by Tiron, a cell-permeable superoxide dismutase (SOD) mimetic and by polyethylene glycol (PEG)-SOD, but not by PEG catalase. Furthermore, insulin-induced O2− production was attenuated by the NAD(P)H inhibitor apocynin, but not by rotenone or oxypurinol. Inhibition of the phosphatidylinositol 3′-kinase (PI 3′-kinase) pathway with LY294002 blocked insulin-stimulated O2− production, suggesting a direct involvement of PI 3′-kinase in the activation of NAD(P)H oxidase. The insulin-induced free radical production led to membranous translocation of p47phox and markedly enhanced ERK-1 and -2 activation in human fibroblasts. In conclusion, these findings provided direct evidence that elevated insulin levels generate O2− by an NAD(P)H-dependent mechanism that involves the activation of PI 3′-kinase and stimulates ERK-1- and ERK-2-dependent pathways. This effect of insulin may contribute to the pathogenesis and progression of cardiovascular disease in the insulin resistance syndrome.</jats:p> Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo Diabetes |
| spellingShingle | Ceolotto, Giulio, Bevilacqua, Michela, Papparella, Italia, Baritono, Elisabetta, Franco, Lorenzo, Corvaja, Carlo, Mazzoni, Martina, Semplicini, Andrea, Avogaro, Angelo, Diabetes, Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo, Endocrinology, Diabetes and Metabolism, Internal Medicine |
| title | Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo |
| title_full | Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo |
| title_fullStr | Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo |
| title_full_unstemmed | Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo |
| title_short | Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo |
| title_sort | insulin generates free radicals by an nad(p)h, phosphatidylinositol 3′-kinase-dependent mechanism in human skin fibroblasts ex vivo |
| title_unstemmed | Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3′-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo |
| topic | Endocrinology, Diabetes and Metabolism, Internal Medicine |
| url | http://dx.doi.org/10.2337/diabetes.53.5.1344 |