PMID- 27866224
OWN - NLM
STAT- MEDLINE
DCOM- 20170828
LR  - 20181202
IS  - 1432-0428 (Electronic)
IS  - 0012-186X (Linking)
VI  - 60
IP  - 2
DP  - 2017 Feb
TI  - The beneficial effects of empagliflozin, an SGLT2 inhibitor, on atherosclerosis 
      in ApoE (-/-) mice fed a western diet.
PG  - 364-376
LID - 10.1007/s00125-016-4158-2 [doi]
AB  - AIMS/HYPOTHESIS: A recent large clinical study has shown that empagliflozin has a 
      lower rate of cardiovascular and all-cause mortality when compared with placebo 
      in patients with type 2 diabetes. We investigated the effect of empagliflozin 
      (compared with glimepiride) on the progression of atherosclerosis, and its 
      possible mechanisms of action. METHODS: Forty-eight 5-week-old male ApoE (-/-) 
      mice were fed a western diet for 20 weeks and divided into four groups: control 
      (saline, 154 mmol/l NaCl), glimepiride 0.1 mg/kg, empagliflozin 1 mg/kg and 
      empagliflozin 3 mg/kg (n = 12/group). Plaque size and composition in the aortic 
      arch/valve areas and cardiovascular risk variables in the blood and tissues were 
      evaluated. Insulin resistance was estimated by HOMA and adiponectin levels. Body 
      composition was determined using dual-energy x-ray absorptiometry. RESULTS: After 
      8 weeks of treatment, the empagliflozin and glimepiride groups exhibited 
      decreased blood glucose levels. Atherosclerotic plaque areas in the aortic 
      arch/valve were significantly smaller in the empagliflozin groups than in the 
      control or glimepiride groups. Insulin resistance and circulating concentrations 
      of TNF-alpha, IL-6, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A and 
      urinary microalbumin decreased after empagliflozin treatment, and this 
      significantly correlated with plaque size. Empagliflozin treatment reduced weight 
      and fat mass, lipid droplets in the liver, fat cell size, mRNA expression of Tnf, 
      Il6 and Mcp-1 (also known as Ccl2) and the infiltration of inflammatory cells in 
      plaque and adipose tissue compared with the control or glimepiride group. 
      Empagliflozin treatment increased adiponectin levels. CONCLUSIONS/INTERPRETATION: 
      Improvements in inflammation and insulin resistance seem to be mechanisms 
      involved in the mitigation of atherosclerosis by empagliflozin.
FAU - Han, Ji Hye
AU  - Han JH
AD  - Department of Internal Medicine, Seoul National University College of Medicine 
      and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, 
      Seongnam-city, South Korea, 463-070.
FAU - Oh, Tae Jung
AU  - Oh TJ
AD  - Department of Internal Medicine, Seoul National University College of Medicine 
      and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, 
      Seongnam-city, South Korea, 463-070.
FAU - Lee, Ghayoung
AU  - Lee G
AD  - Department of Internal Medicine, Seoul National University College of Medicine 
      and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, 
      Seongnam-city, South Korea, 463-070.
FAU - Maeng, Hyo Jin
AU  - Maeng HJ
AD  - Department of Internal Medicine, Seoul National University College of Medicine 
      and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, 
      Seongnam-city, South Korea, 463-070.
FAU - Lee, Dong Hwa
AU  - Lee DH
AD  - Department of Internal Medicine, Seoul National University College of Medicine 
      and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, 
      Seongnam-city, South Korea, 463-070.
FAU - Kim, Kyoung Min
AU  - Kim KM
AD  - Department of Internal Medicine, Seoul National University College of Medicine 
      and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, 
      Seongnam-city, South Korea, 463-070.
FAU - Choi, Sung Hee
AU  - Choi SH
AD  - Department of Internal Medicine, Seoul National University College of Medicine 
      and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, 
      Seongnam-city, South Korea, 463-070.
FAU - Jang, Hak Chul
AU  - Jang HC
AD  - Department of Internal Medicine, Seoul National University College of Medicine 
      and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, 
      Seongnam-city, South Korea, 463-070.
FAU - Lee, Hye Seung
AU  - Lee HS
AD  - Department of Pathology, Seoul National University College of Medicine and Seoul 
      National University Bundang Hospital, Seongnam, South Korea.
FAU - Park, Kyong Soo
AU  - Park KS
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul, South Korea.
FAU - Kim, Young-Bum
AU  - Kim YB
AD  - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth 
      Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
FAU - Lim, Soo
AU  - Lim S
AD  - Department of Internal Medicine, Seoul National University College of Medicine 
      and Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, 
      Seongnam-city, South Korea, 463-070. limsoo@snu.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20161119
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (CD11c Antigen)
RN  - 0 (CD68 antigen, human)
RN  - 0 (Glucosides)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - HDC1R2M35U (empagliflozin)
SB  - IM
MH  - Adipose Tissue/drug effects/metabolism
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Antigens, Differentiation, Myelomonocytic/metabolism
MH  - Apolipoproteins E/genetics/*metabolism
MH  - Atherosclerosis/genetics/*metabolism
MH  - Benzhydryl Compounds/*therapeutic use
MH  - Blotting, Western
MH  - CD11c Antigen/metabolism
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Diabetes Mellitus, Type 2/*drug therapy/etiology/*metabolism
MH  - Diet, Western/*adverse effects
MH  - Glucosides/*therapeutic use
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Insulin Resistance/physiology
MH  - Liver/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Rats
MH  - Real-Time Polymerase Chain Reaction
MH  - *Sodium-Glucose Transporter 2 Inhibitors
OTO - NOTNLM
OT  - Atherosclerosis
OT  - Insulin resistance
OT  - Sodium glucose cotransporter
OT  - Type 2 diabetes
EDAT- 2016/11/21 06:00
MHDA- 2017/08/29 06:00
CRDT- 2016/11/21 06:00
PHST- 2016/09/12 00:00 [received]
PHST- 2016/10/21 00:00 [accepted]
PHST- 2016/11/21 06:00 [pubmed]
PHST- 2017/08/29 06:00 [medline]
PHST- 2016/11/21 06:00 [entrez]
AID - 10.1007/s00125-016-4158-2 [pii]
AID - 10.1007/s00125-016-4158-2 [doi]
PST - ppublish
SO  - Diabetologia. 2017 Feb;60(2):364-376. doi: 10.1007/s00125-016-4158-2. Epub 2016 
      Nov 19.