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Endocrine

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09.02.2016 | Original Article

Blood glucose fluctuation accelerates renal injury involved to inhibit the AKT signaling pathway in diabetic rats

verfasst von: Changjiang Ying, Xiaoyan Zhou, Zhenzhen Chang, Hongwei Ling, Xingbo Cheng, Wei Li

Erschienen in: Endocrine | Ausgabe 1/2016

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Abstract

Blood glucose fluctuation is associated with diabetic nephropathy. However, the mechanism by which blood glucose fluctuation accelerates renal injury is not fully understood. The aim of the present study was to assess the effects of blood glucose fluctuation on diabetic nephropathy in rats and investigate its underlying mechanism. Diabetes in the rats was induced by a high sugar, high-fat diet, and a single dose of STZ (35 mg/kg)-injected intraperitoneally. Unstable blood sugar models were induced by subcutaneous insulin injection and intravenous glucose injection alternately. Body weight, glycosylated hemoglobin A1c (HbAlc), blood urea nitrogen (BUN), serum creatinine (Scr), and Creatinine clearance (Ccr) were assessed. T-SOD activity and MDA level were measured by assay kit. Change in renal tissue ultrastructure was observed by light microscopy and electron microscopy. Phosphorylated ser/thr protein kinase (p-AKT) (phosphor-Ser473), phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β) (phosphor-Ser9), Bcl-2-associated X protein (BAX), B cell lymphoma/leukemia 2 (BCL-2), and cleaved-cysteinyl aspartate-specific proteinase-3 (caspase-3) levels were detected by immunohistochemistry and Western blot. We observed that BUN and Scr were increased in diabetic rats, and Ccr was decreased. Furthermore, blood glucose fluctuations could exacerbate the Ccr changes. Renal tissue ultrastructure was also seriously injured by glucose variability in diabetic rats. In addition, glucose fluctuation increased the oxidative stress of renal tissue. Moreover, fluctuating blood glucose decreased p-AKT level and BCL-2, and increased p-GSK-3β, BAX, cleaved-caspase-3 levels, and ratio of BAX/BCL-2 in the kidneys of diabetic rats. In conclusion, these results suggest that blood glucose fluctuation accelerated renal injury is due, at least in part to its oxidative stress promoting and inhibiting the AKT signaling pathway in diabetic rats.

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Titel: Blood glucose fluctuation accelerates renal injury involved to inhibit the AKT signaling pathway in diabetic rats
verfasst von: Changjiang Ying
Xiaoyan Zhou
Zhenzhen Chang
Hongwei Ling
Xingbo Cheng
Wei Li
Publikationsdatum: 09.02.2016
Verlag: Springer US
Erschienen in: Endocrine / Ausgabe 1/2016
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-016-0867-z

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