Blood glucose fluctuation accelerates renal injury involved to inhibit the AKT signaling pathway in diabetic rats
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ORIGINAL ARTICLE
Blood glucose fluctuation accelerates renal injury involved to inhibit the AKT signaling pathway in diabetic rats Changjiang Ying1,2 • Xiaoyan Zhou3 • Zhenzhen Chang2 • Hongwei Ling2 Xingbo Cheng1 • Wei Li2
•
Received: 24 July 2015 / Accepted: 12 January 2016 Ó Springer Science+Business Media New York 2016
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-3b) (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-3b, 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. Keywords Blood glucose fluctuation Diabetic nephropathy p-AKT Cleaved-caspase-3
Introduction Changjiang Ying, Xiaoyan Zhou, and Zhenzhen Chang have contributed equally to this work. & Xingbo Cheng [email protected] & Wei Li [email protected] 1
Department of Endocrinology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu, People’s Republic of China
2
Department of Endocrinology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu, People’s Republic of China
3
Laboratory of Morphology, Xuzhou Medical College, Xuzhou 221004, Jiangsu, People’s Republic of China
As is well-known, diabetes mellitus (DM) is a type of whole-body chronic metabolic disease with high glucose as the main biochemical ch
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