PMID- 27833913
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2297-055X (Print)
IS  - 2297-055X (Electronic)
IS  - 2297-055X (Linking)
VI  - 3
DP  - 2016
TI  - Glycemic Control with Ipragliflozin, a Novel Selective SGLT2 Inhibitor, 
      Ameliorated Endothelial Dysfunction in Streptozotocin-Induced Diabetic Mouse.
PG  - 43
LID - 43
AB  - BACKGROUND: Endothelial dysfunction caused by increased oxidative stress is a 
      critical initiator of macro- and micro-vascular disease development in diabetic 
      patients. Ipragliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) 
      inhibitor, offers a novel approach for the treatment of diabetes by enhancing 
      urinary glucose excretion. The aim of this study was to examine whether 
      ipragliflozin attenuates endothelial dysfunction in diabetic mice. METHODS: 
      Eight-week-old male C57BL/6 mice were treated with streptozotocin (150 mg/kg) by 
      a single intraperitoneal injection to induce diabetes mellitus. At 3 days of 
      injection, ipragliflozin (3 mg/kg/day) was administered via gavage for 3 weeks. 
      Vascular function was assessed by isometric tension recording. Human umbilical 
      vein endothelial cells (HUVEC) were used for in vitro experiments. RNA and 
      protein expression were examined by quantitative RT-PCR (qPCR) and western blot, 
      respectively. Oxidative stress was determined by measuring urine 
      8-hydroxy-2'-deoxyguanosine (8-OHdG) level. RESULTS: Ipragliflozin administration 
      significantly reduced blood glucose level (P < 0.001) and attenuated the 
      impairment of endothelial function in diabetic mice, as determined by 
      acetylcholine-dependent vasodilation (P < 0.001). Ipragliflozin did not alter 
      metabolic parameters, such as body weight and food intake. Ipragliflozin 
      administration ameliorated impaired phosphorylation of Akt and eNOS(Ser1177) in 
      the abdominal aorta and reduced reactive oxygen species generation as determined 
      by urinary excretion of 8-OHdG in diabetic mice. Furthermore, qPCR analyses 
      demonstrated that ipragliflozin decreased the expression of inflammatory 
      molecules [e.g., monocyte chemoattractant protein-1 (MCP-1) vascular cell 
      adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule (ICAM)-1] in 
      the abdominal aorta (P < 0.05). In in vitro studies, incubation with 
      methylglyoxal, one of the advanced glycation end products, significantly impaired 
      phosphorylation of Akt and eNOS(Ser1177) (P < 0.01) and increased the expression 
      of MCP-1, VCAM-1, and ICAM-1 in HUVEC. CONCLUSION: Ipragliflozin improved 
      hyperglycemia and prevented the development of endothelial dysfunction under a 
      hyperglycemic state, at least partially by attenuation of oxidative stress.
FAU - Salim, Hotimah Masdan
AU  - Salim HM
AD  - Department of Cardiovascular Medicine, Institute of Biomedical Sciences, 
      Tokushima University Graduate School , Tokushima , Japan.
FAU - Fukuda, Daiju
AU  - Fukuda D
AD  - Department of Cardiovascular Medicine, Institute of Biomedical Sciences, 
      Tokushima University Graduate School , Tokushima , Japan.
FAU - Yagi, Shusuke
AU  - Yagi S
AD  - Department of Cardiovascular Medicine, Institute of Biomedical Sciences, 
      Tokushima University Graduate School , Tokushima , Japan.
FAU - Soeki, Takeshi
AU  - Soeki T
AD  - Department of Cardiovascular Medicine, Institute of Biomedical Sciences, 
      Tokushima University Graduate School , Tokushima , Japan.
FAU - Shimabukuro, Michio
AU  - Shimabukuro M
AD  - Department of Cardio-Diabetes Medicine, Institute of Biomedical Sciences, 
      Tokushima University Graduate School , Tokushima , Japan.
FAU - Sata, Masataka
AU  - Sata M
AD  - Department of Cardiovascular Medicine, Institute of Biomedical Sciences, 
      Tokushima University Graduate School , Tokushima , Japan.
LA  - eng
PT  - Journal Article
DEP - 20161026
PL  - Switzerland
TA  - Front Cardiovasc Med
JT  - Frontiers in cardiovascular medicine
JID - 101653388
PMC - PMC5080286
OTO - NOTNLM
OT  - SGLT2 inhibitor
OT  - endothelial function
OT  - hyperglycemia
OT  - inflammation
OT  - oxidative stress
EDAT- 2016/11/12 06:00
MHDA- 2016/11/12 06:01
PMCR- 2016/01/01
CRDT- 2016/11/12 06:00
PHST- 2016/07/22 00:00 [received]
PHST- 2016/10/10 00:00 [accepted]
PHST- 2016/11/12 06:00 [entrez]
PHST- 2016/11/12 06:00 [pubmed]
PHST- 2016/11/12 06:01 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 10.3389/fcvm.2016.00043 [doi]
PST - epublish
SO  - Front Cardiovasc Med. 2016 Oct 26;3:43. doi: 10.3389/fcvm.2016.00043. eCollection 
      2016.