Blood glucose variability can aggravate heart tissue fibrosis, possibly involving oxidative stress by inhibiting AKT signalling path.

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.

Introduction Blood 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 methods Mesangial 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. Results Data 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. Conclusions Glucose fluctuation aggravates mesangial cell apoptosis, which may be partly induced by activating oxidative stress and inhibiting the AKT signaling pathway.

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