• Changjiang Ying, Shanshan Wang, Yan Lu, Lei Chen, Yizhen Mao, Hongwei Ling, Xingbo Cheng, and Xiaoyan Zhou.
• Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
• Arch Med Sci. 2019 May 1; 15 (3): 730-737.

IntroductionBlood glucose fluctuation is an important factor for the development of diabetic complications. Glucose fluctuation aggravated the renal injury in diabetic nephropathy. In the present study, our aim was to investigate the effects of blood glucose fluctuation on the glomerular mesangal cells and its related mechanism.Material And MethodsMesangial cells were divided into four groups: the normal glucose group (NG) cells were incubated in normal glucose conditions (5.6 mmol/l); the high glucose group (HG) cells were treated with 25 mmol/l; the glucose fluctuation (FG) group received 5.6 mmol/l and 25 mmol/l glucose repeated 3 times; the mannitol group (MG) received 5.6 mmol/l glucose plus 24.4 mmol/l mannitol as a control. Cell viability and apoptosis were detected, reactive oxygen species (ROS) level, superoxide dismutase (SOD) activity and malonaldehyde (MDA) levels were measured. Phosphorylated ser/thr protein kinase (P-AKT, phosphor-Ser473), phosphorylated glycogen synthase kinase-3β (P-GSK-3β, phosphor-Ser9) and cleaved cysteinyl aspartate-specific proteinase-3 (cleaved caspase-3) levels were assessed using western blot.ResultsData suggested that mesangial cells in the FG group show higher cell viability in 12 h, and lower cell viability from 48 h. The FG group showed cell apoptosis accompanied by a significant MDA level increase and SOD activity decrease in 48 h. More importantly, glucose fluctuation could aggravate oxidative stress in glomerular mesangial cells. Furthermore, the P-AKT level was lower, and increased P-GSK-3β and cleaved caspase-3 levels were higher in the FG group than in the HG group.ConclusionsGlucose fluctuation aggravates mesangial cell apoptosis, which may be partly induced by activating oxidative stress and inhibiting the AKT signaling pathway.

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