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Long-term alcohol exposure inducing insulin resistance and retinal microvascular damage, a possible role of sphingomyelin
XU Gao-lei WANG Zhi-xin ZHAO Jing-ya CHEN Wen-jing CUI Zhan-jun WANG Yan-fen WANG Hui DENG Jin-bo* GAO Xiao-qun
Acta Anatomica Sinica ›› 2013, Vol. 44 ›› Issue (4) : 441-450.
Long-term alcohol exposure inducing insulin resistance and retinal microvascular damage, a possible role of sphingomyelin
Objective To investigate the mechanism of insulin resistance and retinal damages induced by long-term alcohol
exposure, especially the mechanisms which SM (sphingomyelin, SM) regulationin is involved in. Methods Sphingomyelin synthase
2 knockout (SMS2-/- ) mice and wild type (WT) mice were used to establish the long term alcohol exposure models. The total
cases were 76 in each group. Blood glucose and blood insulin were measured with ELISA assay, in both SMS2-/- mice and WT
mice. In the meantime, homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Finally, the pathologic
alterations about retinal microvasculature were investigated with immunofluorescent labeling, hematoxylin and eosin staining
and electron microscopy. Results Long-term alcohol exposure induced insulin resistance with dose dependency (P <0.05), and
blood retinal barrier (BRB) damages, such as acellular capillaries increased (P <0.05), astrocytes decreased (P <0.05) and
damages of endothelial cell in ultrastrctural level, with dose dependency. In addition, either insulin resistance index
increase or BRB damages in SMS2-/- mice were less than in WT mice (P <0.05), suggesting SMS2-/- mice might attenuate insulin
resistance and BRB damages. Conclusion The insulin resistance (IR) and BRB damages can be induced by long-term alcohol
exposure. As an oxidative stress factor, alcohol exposure may lead to the activation of PKC-NFκB-(Bcl-Xs) pathway and
produce the effects of IR and BRB damages.
Insulin resistance / Alcohol / Retinal capillary / Sphingomyelin / Sphingomyelin synthase 2 / Immunofluorescence / Mouse
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