PMID- 27547413
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160822
LR  - 20220317
IS  - 2052-4897 (Print)
IS  - 2052-4897 (Electronic)
IS  - 2052-4897 (Linking)
VI  - 4
IP  - 1
DP  - 2016
TI  - Dipeptidyl peptidase-4 inhibition by Saxagliptin prevents inflammation and renal 
      injury by targeting the Nlrp3/ASC inflammasome.
PG  - e000227
LID - 10.1136/bmjdrc-2016-000227 [doi]
LID - e000227
AB  - 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 (TNFalpha), interleukin (IL)-1beta, 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, TNFalpha 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.
FAU - Birnbaum, Yochai
AU  - Birnbaum Y
AD  - Department of Biochemistry and Molecular Biology, University of Texas Medical 
      Branch, Galveston, Texas, USA; Section of Cardiology, Department of Medicine, 
      Baylor College of Medicine, Houston, Texas, USA.
FAU - Bajaj, Mandeep
AU  - Bajaj M
AD  - Section of Endocrinology, Department of Medicine , Baylor College of Medicine , 
      Houston, Texas , USA.
FAU - Qian, Jinqiao
AU  - Qian J
AD  - Department of Biochemistry and Molecular Biology, University of Texas Medical 
      Branch, Galveston, Texas, USA; Department of Anesthesiology, First Affiliated 
      Hospital of Kunming Medical University, Kunming, Yunnan, China.
FAU - Ye, Yumei
AU  - Ye Y
AD  - Department of Biochemistry and Molecular Biology , University of Texas Medical 
      Branch , Galveston, Texas , USA.
LA  - eng
PT  - Journal Article
DEP - 20160804
PL  - England
TA  - BMJ Open Diabetes Res Care
JT  - BMJ open diabetes research & care
JID - 101641391
PMC - PMC4985834
OTO - NOTNLM
OT  - Dipeptidyl Peptidase IV
OT  - Experimental Diabetes
OT  - Inflammation and Complications
OT  - Nephropathy
EDAT- 2016/08/23 06:00
MHDA- 2016/08/23 06:01
PMCR- 2016/08/04
CRDT- 2016/08/23 06:00
PHST- 2016/03/16 00:00 [received]
PHST- 2016/06/21 00:00 [revised]
PHST- 2016/06/27 00:00 [accepted]
PHST- 2016/08/23 06:00 [entrez]
PHST- 2016/08/23 06:00 [pubmed]
PHST- 2016/08/23 06:01 [medline]
PHST- 2016/08/04 00:00 [pmc-release]
AID - bmjdrc-2016-000227 [pii]
AID - 10.1136/bmjdrc-2016-000227 [doi]
PST - epublish
SO  - BMJ Open Diabetes Res Care. 2016 Aug 4;4(1):e000227. doi: 
      10.1136/bmjdrc-2016-000227. eCollection 2016.