Exercise ameliorates endothelial dysfunction in type2-diabetic mice through increasing microRNA-181b level via AMPK pathway
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AbstractEndothelial dysfunction plays an essential role in the pathogenesis of diabetic vascular diseases.
Our previous studies showed that exercise ameliorates endothelial dysfunction by inhibiting ER
stress and increasing NO production. AMPK is one of the mediators for the beneficial effect of
exercise in the vasculature. MicroRNA 181b (miR-181b) was reported to improve glucose home-
ostasis and insulin sensitivity by regulating endothelial function. However, whether miR-181b is
regulated by exercise and AMPK remains largely unclear. Therefore, we aim to investigate the
regulation of miR-181b expression by exercise and AMPK and the role of miR-181b in mediating
the beneficial effect of exercise.
Methods and results:
To investigate whether exercise upregulates miR-181b expression, db/db mice were subjected to
treadmill exercise for 45 min per day for two months. Thereafter, mouse aorta was dissected
for real-time PCR. The results show that exercise significantly increases miR-181b expression in
mouse aorta compared to that from control mouse. To examine the impact of blood flow on miR-
181b, human umbilical vein endothelial cells (HUVECs) exposed to laminar flow in a constant
speed at 12 dyn/cm for 24 hours exhibited a dramatical increase of miR-181b expression. To under-
stand the mechanism of miR-181b induction by laminar flow, 5-aminoimidazole-4-carboxamide
ribonucleotide (AICAR) used to treat HUVECs in three separate time points (2, 4, 8 h) signifi-
cantly induced miR-181b expression and peaks at 8 h while compound C remarkably diminished
the AICAR induced miR-181b expression. Consistently, HUVECs transfected with AMPK con-
stitutive activates upregulated miR-181b expression and 2-Deoxy-D-glucose (2-DG) used to treat
HUVECs also induced miR-181b expression. To examine whether miR-181b has beneficial effects
on endothelial function, we over-expressed the miR-181b with adenovirus. The result shows miR-
181b over-expression improved endothelial function in db/db mice accompanied with decreased
vascular inflammation and increased eNOS expression in mouse arteries.
Conclusion:
Exercise ameliorates endothelial dysfunction at least in part through increasing miR-181b level via
AMPK pathway while miR-181b improves endothelial function in diabetic mice by inhibiting vas-
cular inflammation and increasing eNOS expression. MiR-181b may serve as a therapeutic target
for treatment of diabetic vasculopathy.
All Author(s) ListWenbin SHANG, Li WANG, Jiang-Yun LUO, Xiao Yu TIAN, Yu HUANG
Name of ConferenceThe 18th World Congress of Basic and Clinical Pharmacology (WCP2018)
Start Date of Conference01/07/2018
End Date of Conference06/07/2018
Place of ConferenceKyoto, Japan
Country/Region of ConferenceJapan
Year2018
Month7
LanguagesEnglish-United States

Last updated on 2018-27-11 at 17:14