PMID- 31910027
OWN - NLM
STAT- MEDLINE
DCOM- 20200729
LR  - 20211204
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Linking)
VI  - 318
IP  - 5
DP  - 2020 May 1
TI  - Downregulation of microRNA-873 attenuates insulin resistance and myocardial 
      injury in rats with gestational diabetes mellitus by upregulating IGFBP2.
PG  - E723-E735
LID - 10.1152/ajpendo.00555.2018 [doi]
AB  - Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by 
      insulin resistance, and patients with GDM have a higher risk of cardiovascular 
      disease. Multiple microRNAs (miRNAs) are reported to be involved in the 
      regulation of myocardial injury. Moreover, miR-873 was predicted to target 
      insulin-like growth factor binding protein 2 (IGFBP2) through bioinformatic 
      analysis, which was further confirmed using a luciferase assay. Thus, our 
      objective was to assess whether microRNA-873 (miR-873) affects insulin resistance 
      and myocardial injury in an established GDM rat model. The GDM rats were treated 
      with miR-875 mimic or inhibitor or IGFBP2 siRNA. The effects of miR-875 and 
      IGFBP2 on the cardiac function, insulin resistance, and myocardial injury were 
      evaluated by hemodynamic measurements, determination of biochemical indices of 
      myocardium and serum, and insulin homeostatic model assessment. The results 
      indicated that downregulation of miR-873 upregulated the expression of IGFBP2 and 
      promoted the activation of phosphatidylinositol-3 kinase (PI3K)/protein kinase B 
      (AKT)/mammalian target of rapamycin (mTOR) axis. With downregulation of miR-873 
      in GDM rats, the cardiac function was improved and the myocardial apoptosis was 
      inhibited, coupled with elevated activity of superoxide dismutase, carbon 
      monoxide synthase, and the nitric oxide content. In addition, the inhibition of 
      miR-873 in GDM rats modulated the insulin resistance and reduced myocardial 
      apoptosis. Overall, the data showed that inhibition of miR-873 by targeting 
      IGFBP2 may regulate the insulin resistance and curtail myocardial injury in GDM 
      rats through activating the PI3K/AKT/mTOR axis, thus providing a potential means 
      of impeding the progression of GDM.
FAU - Han, Na
AU  - Han N
AD  - Department of Obstetrics, Qingdao Women and Children's Hospital, Qingdao, 
      People's Republic of China.
FAU - Fang, Hai-Yan
AU  - Fang HY
AD  - Department of Obstetrics, Qingdao Women and Children's Hospital, Qingdao, 
      People's Republic of China.
FAU - Jiang, Jie-Xuan
AU  - Jiang JX
AD  - Department of Obstetrics, Qingdao Women and Children's Hospital, Qingdao, 
      People's Republic of China.
FAU - Xu, Qian
AU  - Xu Q
AD  - Department of Obstetrics, Qingdao Women and Children's Hospital, Qingdao, 
      People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20200107
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Insulin-Like Growth Factor Binding Protein 2)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Diabetes, Gestational/genetics/*metabolism
MH  - Down-Regulation
MH  - Female
MH  - *Gene Expression Regulation
MH  - Hemodynamics
MH  - Insulin Resistance/*physiology
MH  - Insulin-Like Growth Factor Binding Protein 2/genetics/*metabolism
MH  - MicroRNAs/genetics/*metabolism
MH  - Myocardial Reperfusion Injury/genetics/*metabolism
MH  - Myocardium/*metabolism
MH  - Pregnancy
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Up-Regulation
OTO - NOTNLM
OT  - PI3K/AKT/mTOR axis
OT  - gestational diabetes mellitus
OT  - insulin resistance
OT  - insulin-like growth factor-binding protein 2
OT  - microRNA-873
OT  - myocardial injury
EDAT- 2020/01/08 06:00
MHDA- 2020/07/30 06:00
CRDT- 2020/01/08 06:00
PHST- 2020/01/08 06:00 [pubmed]
PHST- 2020/07/30 06:00 [medline]
PHST- 2020/01/08 06:00 [entrez]
AID - 10.1152/ajpendo.00555.2018 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2020 May 1;318(5):E723-E735. doi: 
      10.1152/ajpendo.00555.2018. Epub 2020 Jan 7.