机构：[1]Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA[2]Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA[3]Section of Endocrinology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA[4]Department of Anesthesiology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China昆明医科大学附属第一医院外科科室麻醉手术科（医技）
Background: Glucagon-like peptide-1 (GLP-1) receptor activation delays the progression of diabetic nephropathy (DN) in rodents. The NOD-like receptor 3 (Nlrp3) inflammasome plays an important role in DN. Dipeptidyl peptidase-4 inhibitors (DPP4I) inhibit the degradation of endogenous GLP-1 and various other active substances. We assessed whether DPP4I attenuates diabetes-induced activation of the inflammasome and progression of DN in mice with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM). Methods: BTBR (T2DM), Akita (T1DM) and their matched non-diabetic control (wild-type (WT)) mice received 8-week treatment with Saxagliptin (Saxa) or vehicle. Results: Kidney weight and kidney/body weight ratio increased in the BTBR and Akita mice compared to their WT mice. Saxa attenuated these changes in the BTBR, but not in the Akita mice and had no effect in the WT mice. Serum blood urea nitrogen and creatinine significantly increased in the BTBR and Akita mice. Saxa attenuated the increase in the BTBR and Akita mice. Saxa improved glycemic control in the BTBR mice, but had no effect on glucose levels in the Akita and WT mice. Serum C reactive protein, tumor necrosis factor alpha (TNF alpha), interleukin (IL)-1 beta, IL-6 and IL-18 were significantly higher in the BTBR and Akita mice than in the WT mice. Saxa attenuated the increase in the BTBR and Akita mice. Kidney and adipose protein levels of apoptosis-associated speck-like protein 1, NLRP3, TNF alpha and Caspase-1 were higher in the BTBR and Akita mice than in the WT mice. Saxa reduced the levels in both types of diabetic mice. Conclusions: Saxa attenuated diabetes-induced activation of the inflammasome and progression of DN. As Saxa did not affect glucose levels in the Akita mice, these effects are independent of glucose lowering.
基金：
AstraZenecaAstraZeneca; American Diabetes AssociationAmerican Diabetes Association [07-13-TS-04]
第一作者机构：[1]Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA[2]Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
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推荐引用方式(GB/T 7714)：
Birnbaum Yochai,Bajaj Mandeep,Qian Jinqiao,et al.Dipeptidyl peptidase-4 inhibition by Saxagliptin prevents inflammation and renal injury by targeting the Nlrp3/ASC inflammasome[J].BMJ OPEN DIABETES RESEARCH & CARE.2016,4(1):doi:10.1136/bmjdrc-2016-000227.
APA：
Birnbaum, Yochai,Bajaj, Mandeep,Qian, Jinqiao&Ye, Yumei.(2016).Dipeptidyl peptidase-4 inhibition by Saxagliptin prevents inflammation and renal injury by targeting the Nlrp3/ASC inflammasome.BMJ OPEN DIABETES RESEARCH & CARE,4,(1)
MLA：
Birnbaum, Yochai,et al."Dipeptidyl peptidase-4 inhibition by Saxagliptin prevents inflammation and renal injury by targeting the Nlrp3/ASC inflammasome".BMJ OPEN DIABETES RESEARCH & CARE 4..1(2016)
