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Diabetes Res Clin Pract. 2011 Jul;93(1):77-85. doi: 10.1016/j.diabres.2011.03.017. Epub 2011 Apr 13.

Inhibition of ceramide synthesis reverses endothelial dysfunction and atherosclerosis in streptozotocin-induced diabetic rats.

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  • 1Department of Endocrinology, Xiangya Hospital of Central South University, Hunan Province, Xiangya Street 78, Changsha 410008, China.

Abstract

OBJECTIVES:

To explore the effect of myriocin on EDVD and atherosclerosis in diabetic rats.

METHODS:

Rats were fed with a high-fat/high-sucrose/high-cholesterol diet (20% sucrose, 10% animal oil, 1.0% bile salt and 2.5% cholesterol) (hereinafter defined as diabetic groups) or Purina Rodent Chow (NC group), the former was intervened with low dose streptozotocin (30 mg/kg) after feeding 1 month to make diabetic model. The NC group was intervened with citrate buffer and the diabetic rats were intervened with myriocin (0.3 mg/kg Qod) (MTD group) or just solvent (DC group) for 14 weeks. The EDVD, thickness of fatty deposition under endothelium, ceramide, PI3K/PKB/eNOS, NO and other vital parameters were measured after the rats sacrificed.

RESULTS:

In DC group, the ceramide contents in serum and aorta increased, the EDVD was impaired, the fatty deposition under endothelium increased, and the phosphorylation of PI3K/PKB/eNOS and NO release decreased all compared with the NC group (P<0.05). Compared with the DC group, the ceramide contents in MTD group decreased, the EDVD ameliorated, the fatty deposition diminished, and PI3K/PKB/eNOS phosphorylation and NO release (P<0.05) increased.

CONCLUSIONS:

After treated with myriocin, the EDVD in diabetic rats has been improved by increasing PI3K/PKB/eNOS phosphorylation and NO release, and meanwhile the atherosclerosis has reversed.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[PubMed - indexed for MEDLINE]
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