TY - JOUR T1 - Dipeptidyl peptidase-4 inhibition by Saxagliptin prevents inflammation and renal injury by targeting the Nlrp3/ASC inflammasome JF - BMJ Open Diabetes Research & Care JO - BMJ Open Diab Res Care DO - 10.1136/bmjdrc-2016-000227 VL - 4 IS - 1 SP - e000227 AU - Yochai Birnbaum AU - Mandeep Bajaj AU - Jinqiao Qian AU - Yumei Ye Y1 - 2016/08/01 UR - http://drc.bmj.com/content/4/1/e000227.abstract N2 - 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 α (TNFα), interleukin (IL)-1β, 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, TNFα 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. ER -