Troglitazone Has a Scavenging Effect on Reactive Oxygen Species

Inoue, Ituro; Katayama, Shigehiro; Takahashi, Keiichi; Negishi, Kiyohiko; Miyazaki, Takashi; Sonoda, Masaru; Komoda, Tsugikazu

doi:10.1006/bbrc.1997.6512

Cited by 90 publications

(45 citation statements)

References 18 publications

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“…The antioxidant action of TGZ, which is attributable to the similarity of its molecular structure to that of ␣-tocopherol, is considered to be of benefit in preventing diabetic vascular complications, in addition to having hypoglycemic and hypolipidemic effects (29,30). We studied 2-DG uptake in the presence of ␣-tocopherol.…”

Section: Discussionmentioning

confidence: 99%

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Troglitazone Induces GLUT4 Translocation in L6 Myotubes

et al. 2001

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A number of studies have demonstrated that insulin resistance in the skeletal muscle plays a pivotal role in the insulin resistance associated with obesity and type 2 diabetes. A decrease in GLUT4 translocation from the intracellular pool to the plasma membranes in skeletal muscles has been implicated as a possible cause of insulin resistance. Herein, we examined the effects of an insulin-sensitizing drug, troglitazone (TGZ), on glucose uptake and the translocation of GLUT4 in L6 myotubes. The prolonged exposure (24 h) of L6 myotubes to TGZ (10 ؊5 mol/l) caused a substantial increase in the 2-deoxy-[ 3 H]D-glucose (2-DG) uptake without changing the total amount of the glucose transporters GLUT4, GLUT1, and GLUT3. The TGZ-induced 2-DG uptake was completely abolished by cytochalasin-B (10 mol/l). The ability of TGZ to translocate GLUT4 from light microsomes to the crude plasma membranes was greater than that of insulin. Both cycloheximide treatment (3.5 ؋ 10 ؊6 mol/l) and the removal of TGZ by washing reversed the 2-DG uptake to the basal level. Moreover, insulin did not enhance the TGZ-induced 2-DG uptake additively. The TGZ-induced 2-DG uptake was only partially reversed by wortmannin to 80%, and TGZ did not change the expression and the phosphorylation of protein kinase B; the expression of protein kinase C (PKC)-, PKC-␤2, and PKC-; or 5AMP-activated protein kinase activity. ␣-Tocopherol, which has a molecular structure similar to that of TGZ, did not increase 2-DG uptake. We conclude that the glucose transport in L6 myotubes exposed to TGZ for 24 h is the result of an increased translocation of GLUT4. The present results imply that the effects of troglitazone on GLUT4 translocation may include a new mechanism for improving glucose transport in skeletal muscle.

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Section: Discussionmentioning

confidence: 99%

“…Effect of ␣-tocopherol on 2-DG uptake. The action of TGZ may be attributable to the similarity of its molecular structure to that of ␣-tocopherol (29,30). Figure 9 shows that ␣-tocopherol (10 Ϫ5 mol/l, 24 h) did not increase glucose uptake in L6 myotubes.…”

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confidence: 98%

Troglitazone Induces GLUT4 Translocation in L6 Myotubes

et al. 2001

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“…[81][82][83][84][85][86][87] Like vitamin E, TGZ acts as an antioxidant by inhibiting the oxidation of low-density lipoprotein cholesterol and by blocking the reactive products of oxidative stress. 88,89 These antioxidant and anti-inflammatory effects 81,84,88,89 may explain the improved patency of both carotid arteries and coronary artery stents in type 2 diabetic patients who are taking TGZ. 90,91 These beneficial effects of TGZ in patients and animals with insulin resistance are inconsistent with the hypothesis that TGZ induces oxidative stress and mitochondrial abnormalities, 3 except possibly in rare, susceptible individuals.…”

Section: Oxidative Stress and Mitochondrial Damagementioning

confidence: 99%

Troglitazone and liver injury

Chojkier

2005

Hepatology

113

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“…Proliferation was inhibited to the greatest extent with troglitazone (28%) and least, 2%, with tiopronin. Troglitazone, a member of the thiazolidine group, is a newly developed antidiabetic drug with antioxidant activity similar to that of a-tocopherol [16]. Migration was reduced by 73% (p<0.01) following pretreatment with 10-' M EPC-K1, a phosphate di-ester of a-tocopherol and ascorbic acid that inhibits lipid peroxidation [17]; by 64% (p<0.05) by 10-7 M troglitazone; by 41% (p<O.OS) by 10-7 M bucillamine; by 41% by 10_6 M tiopronin; and by 18% by 10-6 M MCLA, an 02 scavenger.…”

Section: Inhibitory Effects Of Antioxidantsmentioning

confidence: 99%