Saxagliptin reduces renal tubulointerstitial inflammation, hypertrophy and fibrosis in diabetes
Saxagliptin reduces renal tubulointerstitial inflammation, hypertrophy and fibrosis in diabetes
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DOI：
10.1111/nep.12618
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发表时间：
2016-05-01
期刊：
影响因子：
2.5
通讯作者：
Panchapakesan, Usha
中科院分区：
文献类型：
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作者：
Komala, Muralikrishna Gangadharan;Gross, Simon;Panchapakesan, Usha
目的除了降低 2 型糖尿病患者的血糖外，二肽基肽酶 4 (DPP4) 抑制剂还被证明具有抗纤维化和抗炎作用。我们之前已经证明，暴露于高葡萄糖的人肾近端肾小管细胞中的 DPP4 抑制可减少纤维化和炎症标志物。因此，我们想在体内模型中证明肾脏保护作用。方法我们使用 1 型糖尿病动物模型来探索沙格列汀独立于葡萄糖降低的肾脏保护潜力。我们使用链脲佐菌素诱导enos -/- 小鼠患糖尿病，并使用胰岛素匹配葡萄糖水平。用沙格列汀治疗糖尿病小鼠，并将结果与未治疗的糖尿病小鼠进行比较。结果我们提供了新的数据，表明沙格列汀限制肾脏肥大、转化生长因子β相关的纤维化和 NF-Bp65 介导的巨噬细胞浸润。总体而言，肾小管间质纤维化的组织学标志物有所减少。蛋白尿或肾小球硬化没有减少。结论我们的研究结果强调了 DPP4 抑制作为额外疗法在解决糖尿病肾病中实现肾脏保护的多种途径方面的潜力。摘要概览作者发现，用 DPP4 抑制剂 Saxagliptin 治疗糖尿病 enos-/- 小鼠可抑制肾小管间质纤维化，与其降糖作用无关，从而凸显了 DDP4 抑制剂的潜力作为糖尿病肾病的辅助治疗。
AimIn addition to lowering blood glucose in patients with type 2 diabetes mellitus, dipeptidyl peptidase 4 (DPP4) inhibitors have been shown to be antifibrotic and anti-inflammatory. We have previously shown that DPP4 inhibition in human kidney proximal tubular cells exposed to high glucose reduced fibrotic and inflammatory markers. Hence, we wanted to demonstrate renoprotection in an in vivo model.MethodsWe used a type 1 diabetic animal model to explore the renoprotective potential of saxagliptin independent of glucose lowering. We induced diabetes in enos -/- mice using streptozotocin and matched glucose levels using insulin. Diabetic mice were treated with saxagliptin and outcomes compared with untreated diabetic mice.ResultsWe provide novel data that saxagliptin limits renal hypertrophy, transforming growth factor beta-related fibrosis and NF-Bp65-mediated macrophage infiltration. Overall, there was a reduction in histological markers of tubulointerstitial fibrosis. There was no reduction in albuminuria or glomerulosclerosis.ConclusionOur findings highlight the potential of DPP4 inhibition as additional therapy in addressing the multiple pathways to achieve renoprotection in diabetic nephropathy.Summary at a Glance The authors found that treatment of diabetic enos-/- mice with the DPP4 inhibitor Saxagliptin led to inhibition of tubulointerstitial fibrosis, independent of its glucose lowering effects, thus highlighting the potential of DDP4 inhibitors as adjunct therapy in diabetic nephropathy.